Publications by authors named "Alexander Hergovich"

63 Publications

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Authors:
Daniel J Klionsky Amal Kamal Abdel-Aziz Sara Abdelfatah Mahmoud Abdellatif Asghar Abdoli Steffen Abel Hagai Abeliovich Marie H Abildgaard Yakubu Princely Abudu Abraham Acevedo-Arozena Iannis E Adamopoulos Khosrow Adeli Timon E Adolph Annagrazia Adornetto Elma Aflaki Galila Agam Anupam Agarwal Bharat B Aggarwal Maria Agnello Patrizia Agostinis Javed N Agrewala Alexander Agrotis Patricia V Aguilar S Tariq Ahmad Zubair M Ahmed Ulises Ahumada-Castro Sonja Aits Shu Aizawa Yunus Akkoc Tonia Akoumianaki Hafize Aysin Akpinar Ahmed M Al-Abd Lina Al-Akra Abeer Al-Gharaibeh Moulay A Alaoui-Jamali Simon Alberti Elísabet Alcocer-Gómez Cristiano Alessandri Muhammad Ali M Abdul Alim Al-Bari Saeb Aliwaini Javad Alizadeh Eugènia Almacellas Alexandru Almasan Alicia Alonso Guillermo D Alonso Nihal Altan-Bonnet Dario C Altieri Élida M C Álvarez Sara Alves Cristine Alves da Costa Mazen M Alzaharna Marialaura Amadio Consuelo Amantini Cristina Amaral Susanna Ambrosio Amal O Amer Veena Ammanathan Zhenyi An Stig U Andersen Shaida A Andrabi Magaiver Andrade-Silva Allen M Andres Sabrina Angelini David Ann Uche C Anozie Mohammad Y Ansari Pedro Antas Adam Antebi Zuriñe Antón Tahira Anwar Lionel Apetoh Nadezda Apostolova Toshiyuki Araki Yasuhiro Araki Kohei Arasaki Wagner L Araújo Jun Araya Catherine Arden Maria-Angeles Arévalo Sandro Arguelles Esperanza Arias Jyothi Arikkath Hirokazu Arimoto Aileen R Ariosa Darius Armstrong-James Laetitia Arnauné-Pelloquin Angeles Aroca Daniela S Arroyo Ivica Arsov Rubén Artero Dalia Maria Lucia Asaro Michael Aschner Milad Ashrafizadeh Osnat Ashur-Fabian Atanas G Atanasov Alicia K Au Patrick Auberger Holger W Auner Laure Aurelian Riccardo Autelli Laura Avagliano Yenniffer Ávalos Sanja Aveic Célia Alexandra Aveleira Tamar Avin-Wittenberg Yucel Aydin Scott Ayton Srinivas Ayyadevara Maria Azzopardi Misuzu Baba Jonathan M Backer Steven K Backues Dong-Hun Bae Ok-Nam Bae Soo Han Bae Eric H Baehrecke Ahruem Baek Seung-Hoon Baek Sung Hee Baek Giacinto Bagetta Agnieszka Bagniewska-Zadworna Hua Bai Jie Bai Xiyuan Bai Yidong Bai Nandadulal Bairagi Shounak Baksi Teresa Balbi Cosima T Baldari Walter Balduini Andrea Ballabio Maria Ballester Salma Balazadeh Rena Balzan Rina Bandopadhyay Sreeparna Banerjee Sulagna Banerjee Ágnes Bánréti Yan Bao Mauricio S Baptista Alessandra Baracca Cristiana Barbati Ariadna Bargiela Daniela Barilà Peter G Barlow Sami J Barmada Esther Barreiro George E Barreto Jiri Bartek Bonnie Bartel Alberto Bartolome Gaurav R Barve Suresh H Basagoudanavar Diane C Bassham Robert C Bast Alakananda Basu Henri Batoko Isabella Batten Etienne E Baulieu Bradley L Baumgarner Jagadeesh Bayry Rupert Beale Isabelle Beau Florian Beaumatin Luiz R G Bechara George R Beck Michael F Beers Jakob Begun Christian Behrends Georg M N Behrens Roberto Bei Eloy Bejarano Shai Bel Christian Behl Amine Belaid Naïma Belgareh-Touzé Cristina Bellarosa Francesca Belleudi Melissa Belló Pérez Raquel Bello-Morales Jackeline Soares de Oliveira Beltran Sebastián Beltran Doris Mangiaracina Benbrook Mykolas Bendorius Bruno A Benitez Irene Benito-Cuesta Julien Bensalem Martin W Berchtold Sabina Berezowska Daniele Bergamaschi Matteo Bergami Andreas Bergmann Laura Berliocchi Clarisse Berlioz-Torrent Amélie Bernard Lionel Berthoux Cagri G Besirli Sebastien Besteiro Virginie M Betin Rudi Beyaert Jelena S Bezbradica Kiran Bhaskar Ingrid Bhatia-Kissova Resham Bhattacharya Sujoy Bhattacharya Shalmoli Bhattacharyya Md Shenuarin Bhuiyan Sujit Kumar Bhutia Lanrong Bi Xiaolin Bi Trevor J Biden Krikor Bijian Viktor A Billes Nadine Binart Claudia Bincoletto Asa B Birgisdottir Geir Bjorkoy Gonzalo Blanco Ana Blas-Garcia Janusz Blasiak Robert Blomgran Klas Blomgren Janice S Blum Emilio Boada-Romero Mirta Boban Kathleen Boesze-Battaglia Philippe Boeuf Barry Boland Pascale Bomont Paolo Bonaldo Srinivasa Reddy Bonam Laura Bonfili Juan S Bonifacino Brian A Boone Martin D Bootman Matteo Bordi Christoph Borner Beat C Bornhauser Gautam Borthakur Jürgen Bosch Santanu Bose Luis M Botana Juan Botas Chantal M Boulanger Michael E Boulton Mathieu Bourdenx Benjamin Bourgeois Nollaig M Bourke Guilhem Bousquet Patricia Boya Peter V Bozhkov Luiz H M Bozi Tolga O Bozkurt Doug E Brackney Christian H Brandts Ralf J Braun Gerhard H Braus Roberto Bravo-Sagua José M Bravo-San Pedro Patrick Brest Marie-Agnès Bringer Alfredo Briones-Herrera V Courtney Broaddus Peter Brodersen Jeffrey L Brodsky Steven L Brody Paola G Bronson Jeff M Bronstein Carolyn N Brown Rhoderick E Brown Patricia C Brum John H Brumell Nicola Brunetti-Pierri Daniele Bruno Robert J Bryson-Richardson Cecilia Bucci Carmen Buchrieser Marta Bueno Laura Elisa Buitrago-Molina Simone Buraschi Shilpa Buch J Ross Buchan Erin M Buckingham Hikmet Budak Mauricio Budini Geert Bultynck Florin Burada Joseph R Burgoyne M Isabel Burón Victor Bustos Sabrina Büttner Elena Butturini Aaron Byrd Isabel Cabas Sandra Cabrera-Benitez Ken Cadwell Jingjing Cai Lu Cai Qian Cai Montserrat Cairó Jose A Calbet Guy A Caldwell Kim A Caldwell Jarrod A Call Riccardo Calvani Ana C Calvo Miguel Calvo-Rubio Barrera Niels Os Camara Jacques H Camonis Nadine Camougrand Michelangelo Campanella Edward M Campbell François-Xavier Campbell-Valois Silvia Campello Ilaria Campesi Juliane C Campos Olivier Camuzard Jorge Cancino Danilo Candido de Almeida Laura Canesi Isabella Caniggia Barbara Canonico Carles Cantí Bin Cao Michele Caraglia Beatriz Caramés Evie H Carchman Elena Cardenal-Muñoz Cesar Cardenas Luis Cardenas Sandra M Cardoso Jennifer S Carew Georges F Carle Gillian Carleton Silvia Carloni Didac Carmona-Gutierrez Leticia A Carneiro Oliana Carnevali Julian M Carosi Serena Carra Alice Carrier Lucie Carrier Bernadette Carroll A Brent Carter Andreia Neves Carvalho Magali Casanova Caty Casas Josefina Casas Chiara Cassioli Eliseo F Castillo Karen Castillo Sonia Castillo-Lluva Francesca Castoldi Marco Castori Ariel F Castro Margarida Castro-Caldas Javier Castro-Hernandez Susana Castro-Obregon Sergio D Catz Claudia Cavadas Federica Cavaliere Gabriella Cavallini Maria Cavinato Maria L Cayuela Paula Cebollada Rica Valentina Cecarini Francesco Cecconi Marzanna Cechowska-Pasko Simone Cenci Victòria Ceperuelo-Mallafré João J Cerqueira Janete M Cerutti Davide Cervia Vildan Bozok Cetintas Silvia Cetrullo Han-Jung Chae Andrei S Chagin Chee-Yin Chai Gopal Chakrabarti Oishee Chakrabarti Tapas Chakraborty Trinad Chakraborty Mounia Chami Georgios Chamilos David W Chan Edmond Y W Chan Edward D Chan H Y Edwin Chan Helen H Chan Hung Chan Matthew T V Chan Yau Sang Chan Partha K Chandra Chih-Peng Chang Chunmei Chang Hao-Chun Chang Kai Chang Jie Chao Tracey Chapman Nicolas Charlet-Berguerand Samrat Chatterjee Shail K Chaube Anu Chaudhary Santosh Chauhan Edward Chaum Frédéric Checler Michael E Cheetham Chang-Shi Chen Guang-Chao Chen Jian-Fu Chen Liam L Chen Leilei Chen Lin Chen Mingliang Chen Mu-Kuan Chen Ning Chen Quan Chen Ruey-Hwa Chen Shi Chen Wei Chen Weiqiang Chen Xin-Ming Chen Xiong-Wen Chen Xu Chen Yan Chen Ye-Guang Chen Yingyu Chen Yongqiang Chen Yu-Jen Chen Yue-Qin Chen Zhefan Stephen Chen Zhi Chen Zhi-Hua Chen Zhijian J Chen Zhixiang Chen Hanhua Cheng Jun Cheng Shi-Yuan Cheng Wei Cheng Xiaodong Cheng Xiu-Tang Cheng Yiyun Cheng Zhiyong Cheng Zhong Chen Heesun Cheong Jit Kong Cheong Boris V Chernyak Sara Cherry Chi Fai Randy Cheung Chun Hei Antonio Cheung King-Ho Cheung Eric Chevet Richard J Chi Alan Kwok Shing Chiang Ferdinando Chiaradonna Roberto Chiarelli Mario Chiariello Nathalia Chica Susanna Chiocca Mario Chiong Shih-Hwa Chiou Abhilash I Chiramel Valerio Chiurchiù Dong-Hyung Cho Seong-Kyu Choe Augustine M K Choi Mary E Choi Kamalika Roy Choudhury Norman S Chow Charleen T Chu Jason P Chua John Jia En Chua Hyewon Chung Kin Pan Chung Seockhoon Chung So-Hyang Chung Yuen-Li Chung Valentina Cianfanelli Iwona A Ciechomska Mariana Cifuentes Laura Cinque Sebahattin Cirak Mara Cirone Michael J Clague Robert Clarke Emilio Clementi Eliana M Coccia Patrice Codogno Ehud Cohen Mickael M Cohen Tania Colasanti Fiorella Colasuonno Robert A Colbert Anna Colell Miodrag Čolić Nuria S Coll Mark O Collins María I Colombo Daniel A Colón-Ramos Lydie Combaret Sergio Comincini Márcia R Cominetti Antonella Consiglio Andrea Conte Fabrizio Conti Viorica Raluca Contu Mark R Cookson Kevin M Coombs Isabelle Coppens Maria Tiziana Corasaniti Dale P Corkery Nils Cordes Katia Cortese Maria do Carmo Costa Sarah Costantino Paola Costelli Ana Coto-Montes Peter J Crack Jose L Crespo Alfredo Criollo Valeria Crippa Riccardo Cristofani Tamas Csizmadia Antonio Cuadrado Bing Cui Jun Cui Yixian Cui Yong Cui Emmanuel Culetto Andrea C Cumino Andrey V Cybulsky Mark J Czaja Stanislaw J Czuczwar Stefania D'Adamo Marcello D'Amelio Daniela D'Arcangelo Andrew C D'Lugos Gabriella D'Orazi James A da Silva Hormos Salimi Dafsari Ruben K Dagda Yasin Dagdas Maria Daglia Xiaoxia Dai Yun Dai Yuyuan Dai Jessica Dal Col Paul Dalhaimer Luisa Dalla Valle Tobias Dallenga Guillaume Dalmasso Markus Damme Ilaria Dando Nico P Dantuma April L Darling Hiranmoy Das Srinivasan Dasarathy Santosh K Dasari Srikanta Dash Oliver Daumke Adrian N Dauphinee Jeffrey S Davies Valeria A Dávila Roger J Davis Tanja Davis Sharadha Dayalan Naidu Francesca De Amicis Karolien De Bosscher Francesca De Felice Lucia De Franceschi Chiara De Leonibus Mayara G de Mattos Barbosa Guido R Y De Meyer Angelo De Milito Cosimo De Nunzio Clara De Palma Mauro De Santi Claudio De Virgilio Daniela De Zio Jayanta Debnath Brian J DeBosch Jean-Paul Decuypere Mark A Deehan Gianluca Deflorian James DeGregori Benjamin Dehay Gabriel Del Rio Joe R Delaney Lea M D Delbridge Elizabeth Delorme-Axford M Victoria Delpino Francesca Demarchi Vilma Dembitz Nicholas D Demers Hongbin Deng Zhiqiang Deng Joern Dengjel Paul Dent Donna Denton Melvin L DePamphilis Channing J Der Vojo Deretic Albert Descoteaux Laura Devis Sushil Devkota Olivier Devuyst Grant Dewson Mahendiran Dharmasivam Rohan Dhiman Diego di Bernardo Manlio Di Cristina Fabio Di Domenico Pietro Di Fazio Alessio Di Fonzo Giovanni Di Guardo Gianni M Di Guglielmo Luca Di Leo Chiara Di Malta Alessia Di Nardo Martina Di Rienzo Federica Di Sano George Diallinas Jiajie Diao Guillermo Diaz-Araya Inés Díaz-Laviada Jared M Dickinson Marc Diederich Mélanie Dieudé Ivan Dikic Shiping Ding Wen-Xing Ding Luciana Dini Jelena Dinić Miroslav Dinic Albena T Dinkova-Kostova Marc S Dionne Jörg H W Distler Abhinav Diwan Ian M C Dixon Mojgan Djavaheri-Mergny Ina Dobrinski Oxana Dobrovinskaya Radek Dobrowolski Renwick C J Dobson Jelena Đokić Serap Dokmeci Emre Massimo Donadelli Bo Dong Xiaonan Dong Zhiwu Dong Gerald W Dorn Ii Volker Dotsch Huan Dou Juan Dou Moataz Dowaidar Sami Dridi Liat Drucker Ailian Du Caigan Du Guangwei Du Hai-Ning Du Li-Lin Du André du Toit Shao-Bin Duan Xiaoqiong Duan Sónia P Duarte Anna Dubrovska Elaine A Dunlop Nicolas Dupont Raúl V Durán Bilikere S Dwarakanath Sergey A Dyshlovoy Darius Ebrahimi-Fakhari Leopold Eckhart Charles L Edelstein Thomas Efferth Eftekhar Eftekharpour Ludwig Eichinger Nabil Eid Tobias Eisenberg N Tony Eissa Sanaa Eissa Miriam Ejarque Abdeljabar El Andaloussi Nazira El-Hage Shahenda El-Naggar Anna Maria Eleuteri Eman S El-Shafey Mohamed Elgendy Aristides G Eliopoulos María M Elizalde Philip M Elks Hans-Peter Elsasser Eslam S Elsherbiny Brooke M Emerling N C Tolga Emre Christina H Eng Nikolai Engedal Anna-Mart Engelbrecht Agnete S T Engelsen Jorrit M Enserink Ricardo Escalante Audrey Esclatine Mafalda Escobar-Henriques Eeva-Liisa Eskelinen Lucile Espert Makandjou-Ola Eusebio Gemma Fabrias Cinzia Fabrizi Antonio Facchiano Francesco Facchiano Bengt Fadeel Claudio Fader Alex C Faesen W Douglas Fairlie Alberto Falcó Bjorn H Falkenburger Daping Fan Jie Fan Yanbo Fan Evandro F Fang Yanshan Fang Yognqi Fang Manolis Fanto Tamar Farfel-Becker Mathias Faure Gholamreza Fazeli Anthony O Fedele Arthur M Feldman Du Feng Jiachun Feng Lifeng Feng Yibin Feng Yuchen Feng Wei Feng Thais Fenz Araujo Thomas A Ferguson Álvaro F Fernández Jose C Fernandez-Checa Sonia Fernández-Veledo Alisdair R Fernie Anthony W Ferrante Alessandra Ferraresi Merari F Ferrari Julio C B Ferreira Susan Ferro-Novick Antonio Figueras Riccardo Filadi Nicoletta Filigheddu Eduardo Filippi-Chiela Giuseppe Filomeni Gian Maria Fimia Vittorio Fineschi Francesca Finetti Steven Finkbeiner Edward A Fisher Paul B Fisher Flavio Flamigni Steven J Fliesler Trude H Flo Ida Florance Oliver Florey Tullio Florio Erika Fodor Carlo Follo Edward A Fon Antonella Forlino Francesco Fornai Paola Fortini Anna Fracassi Alessandro Fraldi Brunella Franco Rodrigo Franco Flavia Franconi Lisa B Frankel Scott L Friedman Leopold F Fröhlich Gema Frühbeck Jose M Fuentes Yukio Fujiki Naonobu Fujita Yuuki Fujiwara Mitsunori Fukuda Simone Fulda Luc Furic Norihiko Furuya Carmela Fusco Michaela U Gack Lidia Gaffke Sehamuddin Galadari Alessia Galasso Maria F Galindo Sachith Gallolu Kankanamalage Lorenzo Galluzzi Vincent Galy Noor Gammoh Boyi Gan Ian G Ganley Feng Gao Hui Gao Minghui Gao Ping Gao Shou-Jiang Gao Wentao Gao Xiaobo Gao Ana Garcera Maria Noé Garcia Verónica E Garcia Francisco García-Del Portillo Vega Garcia-Escudero Aracely Garcia-Garcia Marina Garcia-Macia Diana García-Moreno Carmen Garcia-Ruiz Patricia García-Sanz Abhishek D Garg Ricardo Gargini Tina Garofalo Robert F Garry Nils C Gassen Damian Gatica Liang Ge Wanzhong Ge Ruth Geiss-Friedlander Cecilia Gelfi Pascal Genschik Ian E Gentle Valeria Gerbino Christoph Gerhardt Kyla Germain Marc Germain David A Gewirtz Elham Ghasemipour Afshar Saeid Ghavami Alessandra Ghigo Manosij Ghosh Georgios Giamas Claudia Giampietri Alexandra Giatromanolaki Gary E Gibson Spencer B Gibson Vanessa Ginet Edward Giniger Carlotta Giorgi Henrique Girao Stephen E Girardin Mridhula Giridharan Sandy Giuliano Cecilia Giulivi Sylvie Giuriato Julien Giustiniani Alexander Gluschko Veit Goder Alexander Goginashvili Jakub Golab David C Goldstone Anna Golebiewska Luciana R Gomes Rodrigo Gomez Rubén Gómez-Sánchez Maria Catalina Gomez-Puerto Raquel Gomez-Sintes Qingqiu Gong Felix M Goni Javier González-Gallego Tomas Gonzalez-Hernandez Rosa A Gonzalez-Polo Jose A Gonzalez-Reyes Patricia González-Rodríguez Ing Swie Goping Marina S Gorbatyuk Nikolai V Gorbunov Kıvanç Görgülü Roxana M Gorojod Sharon M Gorski Sandro Goruppi Cecilia Gotor Roberta A Gottlieb Illana Gozes Devrim Gozuacik Martin Graef Markus H Gräler Veronica Granatiero Daniel Grasso Joshua P Gray Douglas R Green Alexander Greenhough Stephen L Gregory Edward F Griffin Mark W Grinstaff Frederic Gros Charles Grose Angelina S Gross Florian Gruber Paolo Grumati Tilman Grune Xueyan Gu Jun-Lin Guan Carlos M Guardia Kishore Guda Flora Guerra Consuelo Guerri Prasun Guha Carlos Guillén Shashi Gujar Anna Gukovskaya Ilya Gukovsky Jan Gunst Andreas Günther Anyonya R Guntur Chuanyong Guo Chun Guo Hongqing Guo Lian-Wang Guo Ming Guo Pawan Gupta Shashi Kumar Gupta Swapnil Gupta Veer Bala Gupta Vivek Gupta Asa B Gustafsson David D Gutterman Ranjitha H B Annakaisa Haapasalo James E Haber Aleksandra Hać Shinji Hadano Anders J Hafrén Mansour Haidar Belinda S Hall Gunnel Halldén Anne Hamacher-Brady Andrea Hamann Maho Hamasaki Weidong Han Malene Hansen Phyllis I Hanson Zijian Hao Masaru Harada Ljubica Harhaji-Trajkovic Nirmala Hariharan Nigil Haroon James Harris Takafumi Hasegawa Noor Hasima Nagoor Jeffrey A Haspel Volker Haucke Wayne D Hawkins Bruce A Hay Cole M Haynes Soren B Hayrabedyan Thomas S Hays Congcong He Qin He Rong-Rong He You-Wen He Yu-Ying He Yasser Heakal Alexander M Heberle J Fielding Hejtmancik Gudmundur Vignir Helgason Vanessa Henkel Marc Herb Alexander Hergovich Anna Herman-Antosiewicz Agustín Hernández Carlos Hernandez Sergio Hernandez-Diaz Virginia Hernandez-Gea Amaury Herpin Judit Herreros Javier H Hervás Daniel Hesselson Claudio Hetz Volker T Heussler Yujiro Higuchi Sabine Hilfiker Joseph A Hill William S Hlavacek Emmanuel A Ho Idy H T Ho Philip Wing-Lok Ho Shu-Leong Ho Wan Yun Ho G Aaron Hobbs Mark Hochstrasser Peter H M Hoet Daniel Hofius Paul Hofman Annika Höhn Carina I Holmberg Jose R Hombrebueno Chang-Won Hong Yi-Ren Hong Lora V Hooper Thorsten Hoppe Rastislav Horos Yujin Hoshida I-Lun Hsin Hsin-Yun Hsu Bing Hu Dong Hu Li-Fang Hu Ming Chang Hu Ronggui Hu Wei Hu Yu-Chen Hu Zhuo-Wei Hu Fang Hua Jinlian Hua Yingqi Hua Chongmin Huan Canhua Huang Chuanshu Huang Chuanxin Huang Chunling Huang Haishan Huang Kun Huang Michael L H Huang Rui Huang Shan Huang Tianzhi Huang Xing Huang Yuxiang Jack Huang Tobias B Huber Virginie Hubert Christian A Hubner Stephanie M Hughes William E Hughes Magali Humbert Gerhard Hummer James H Hurley Sabah Hussain Salik Hussain Patrick J Hussey Martina Hutabarat Hui-Yun Hwang Seungmin Hwang Antonio Ieni Fumiyo Ikeda Yusuke Imagawa Yuzuru Imai Carol Imbriano Masaya Imoto Denise M Inman Ken Inoki Juan Iovanna Renato V Iozzo Giuseppe Ippolito Javier E Irazoqui Pablo Iribarren Mohd Ishaq Makoto Ishikawa Nestor Ishimwe Ciro Isidoro Nahed Ismail Shohreh Issazadeh-Navikas Eisuke Itakura Daisuke Ito Davor Ivankovic Saška Ivanova Anand Krishnan V Iyer José M Izquierdo Masanori Izumi Marja Jäättelä Majid Sakhi Jabir William T Jackson Nadia Jacobo-Herrera Anne-Claire Jacomin Elise Jacquin Pooja Jadiya Hartmut Jaeschke Chinnaswamy Jagannath Arjen J Jakobi Johan Jakobsson Bassam Janji Pidder Jansen-Dürr Patric J Jansson Jonathan Jantsch Sławomir Januszewski Alagie Jassey Steve Jean Hélène Jeltsch-David Pavla Jendelova Andreas Jenny Thomas E Jensen Niels Jessen Jenna L Jewell Jing Ji Lijun Jia Rui Jia Liwen Jiang Qing Jiang Richeng Jiang Teng Jiang Xuejun Jiang Yu Jiang Maria Jimenez-Sanchez Eun-Jung Jin Fengyan Jin Hongchuan Jin Li Jin Luqi Jin Meiyan Jin Si Jin Eun-Kyeong Jo Carine Joffre Terje Johansen Gail V W Johnson Simon A Johnston Eija Jokitalo Mohit Kumar Jolly Leo A B Joosten Joaquin Jordan Bertrand Joseph Dianwen Ju Jeong-Sun Ju Jingfang Ju Esmeralda Juárez Delphine Judith Gábor Juhász Youngsoo Jun Chang Hwa Jung Sung-Chul Jung Yong Keun Jung Heinz Jungbluth Johannes Jungverdorben Steffen Just Kai Kaarniranta Allen Kaasik Tomohiro Kabuta Daniel Kaganovich Alon Kahana Renate Kain Shinjo Kajimura Maria Kalamvoki Manjula Kalia Danuta S Kalinowski Nina Kaludercic Ioanna Kalvari Joanna Kaminska Vitaliy O Kaminskyy Hiromitsu Kanamori Keizo Kanasaki Chanhee Kang Rui Kang Sang Sun Kang Senthilvelrajan Kaniyappan Tomotake Kanki Thirumala-Devi Kanneganti Anumantha G Kanthasamy Arthi Kanthasamy Marc Kantorow Orsolya Kapuy Michalis V Karamouzis Md Razaul Karim Parimal Karmakar Rajesh G Katare Masaru Kato Stefan H E Kaufmann Anu Kauppinen Gur P Kaushal Susmita Kaushik Kiyoshi Kawasaki Kemal Kazan Po-Yuan Ke Damien J Keating Ursula Keber John H Kehrl Kate E Keller Christian W Keller Jongsook Kim Kemper Candia M Kenific Oliver Kepp Stephanie Kermorgant Andreas Kern Robin Ketteler Tom G Keulers Boris Khalfin Hany Khalil Bilon Khambu Shahid Y Khan Vinoth Kumar Megraj Khandelwal Rekha Khandia Widuri Kho Noopur V Khobrekar Sataree Khuansuwan Mukhran Khundadze Samuel A Killackey Dasol Kim Deok Ryong Kim Do-Hyung Kim Dong-Eun Kim Eun Young Kim Eun-Kyoung Kim Hak-Rim Kim Hee-Sik Kim Hyung-Ryong Kim Jeong Hun Kim Jin Kyung Kim Jin-Hoi Kim Joungmok Kim Ju Hwan Kim Keun Il Kim Peter K Kim Seong-Jun Kim Scot R Kimball Adi Kimchi Alec C Kimmelman Tomonori Kimura Matthew A King Kerri J Kinghorn Conan G Kinsey Vladimir Kirkin Lorrie A Kirshenbaum Sergey L Kiselev Shuji Kishi Katsuhiko Kitamoto Yasushi Kitaoka Kaio Kitazato Richard N Kitsis Josef T Kittler Ole Kjaerulff Peter S Klein Thomas Klopstock Jochen Klucken Helene Knævelsrud Roland L Knorr Ben C B Ko Fred Ko Jiunn-Liang Ko Hotaka Kobayashi Satoru Kobayashi Ina Koch Jan C Koch Ulrich Koenig Donat Kögel Young Ho Koh Masato Koike Sepp D Kohlwein Nur M Kocaturk Masaaki Komatsu Jeannette König Toru Kono Benjamin T Kopp Tamas Korcsmaros Gözde Korkmaz Viktor I Korolchuk Mónica Suárez Korsnes Ali Koskela Janaiah Kota Yaichiro Kotake Monica L Kotler Yanjun Kou Michael I Koukourakis Evangelos Koustas Attila L Kovacs Tibor Kovács Daisuke Koya Tomohiro Kozako Claudine Kraft Dimitri Krainc Helmut Krämer Anna D Krasnodembskaya Carole Kretz-Remy Guido Kroemer Nicholas T Ktistakis Kazuyuki Kuchitsu Sabine Kuenen Lars Kuerschner Thomas Kukar Ajay Kumar Ashok Kumar Deepak Kumar Dhiraj Kumar Sharad Kumar Shinji Kume Caroline Kumsta Chanakya N Kundu Mondira Kundu Ajaikumar B Kunnumakkara Lukasz Kurgan Tatiana G Kutateladze Ozlem Kutlu SeongAe Kwak Ho Jeong Kwon Taeg Kyu Kwon Yong Tae Kwon Irene Kyrmizi Albert La Spada Patrick Labonté Sylvain Ladoire Ilaria Laface Frank Lafont Diane C Lagace Vikramjit Lahiri Zhibing Lai Angela S Laird Aparna Lakkaraju Trond Lamark Sheng-Hui Lan Ane Landajuela Darius J R Lane Jon D Lane Charles H Lang Carsten Lange Ülo Langel Rupert Langer Pierre Lapaquette Jocelyn Laporte Nicholas F LaRusso Isabel Lastres-Becker Wilson Chun Yu Lau Gordon W Laurie Sergio Lavandero Betty Yuen Kwan Law Helen Ka-Wai Law Rob Layfield Weidong Le Herve Le Stunff Alexandre Y Leary Jean-Jacques Lebrun Lionel Y W Leck Jean-Philippe Leduc-Gaudet Changwook Lee Chung-Pei Lee Da-Hye Lee Edward B Lee Erinna F Lee Gyun Min Lee He-Jin Lee Heung Kyu Lee Jae Man Lee Jason S Lee Jin-A Lee Joo-Yong Lee Jun Hee Lee Michael Lee Min Goo Lee Min Jae Lee Myung-Shik Lee Sang Yoon Lee Seung-Jae Lee Stella Y Lee Sung Bae Lee Won Hee Lee Ying-Ray Lee Yong-Ho Lee Youngil Lee Christophe Lefebvre Renaud Legouis Yu L Lei Yuchen Lei Sergey Leikin Gerd Leitinger Leticia Lemus Shuilong Leng Olivia Lenoir Guido Lenz Heinz Josef Lenz Paola Lenzi Yolanda León Andréia M Leopoldino Christoph Leschczyk Stina Leskelä Elisabeth Letellier Chi-Ting Leung Po Sing Leung Jeremy S Leventhal Beth Levine Patrick A Lewis Klaus Ley Bin Li Da-Qiang Li Jianming Li Jing Li Jiong Li Ke Li Liwu Li Mei Li Min Li Min Li Ming Li Mingchuan Li Pin-Lan Li Ming-Qing Li Qing Li Sheng Li Tiangang Li Wei Li Wenming Li Xue Li Yi-Ping Li Yuan Li Zhiqiang Li Zhiyong Li Zhiyuan Li Jiqin Lian Chengyu Liang Qiangrong Liang Weicheng Liang Yongheng Liang YongTian Liang Guanghong Liao Lujian Liao Mingzhi Liao Yung-Feng Liao Mariangela Librizzi Pearl P Y Lie Mary A Lilly Hyunjung J Lim Thania R R Lima Federica Limana Chao Lin Chih-Wen Lin Dar-Shong Lin Fu-Cheng Lin Jiandie D Lin Kurt M Lin Kwang-Huei Lin Liang-Tzung Lin Pei-Hui Lin Qiong Lin Shaofeng Lin Su-Ju Lin Wenyu Lin Xueying Lin Yao-Xin Lin Yee-Shin Lin Rafael Linden Paula Lindner Shuo-Chien Ling Paul Lingor Amelia K Linnemann Yih-Cherng Liou Marta M Lipinski Saška Lipovšek Vitor A Lira Natalia Lisiak Paloma B Liton Chao Liu Ching-Hsuan Liu Chun-Feng Liu Cui Hua Liu Fang Liu Hao Liu Hsiao-Sheng Liu Hua-Feng Liu Huifang Liu Jia Liu Jing Liu Julia Liu Leyuan Liu Longhua Liu Meilian Liu Qin Liu Wei Liu Wende Liu Xiao-Hong Liu Xiaodong Liu Xingguo Liu Xu Liu Xuedong Liu Yanfen Liu Yang Liu Yang Liu Yueyang Liu Yule Liu J Andrew Livingston Gerard Lizard Jose M Lizcano Senka Ljubojevic-Holzer Matilde E LLeonart David Llobet-Navàs Alicia Llorente Chih Hung Lo Damián Lobato-Márquez Qi Long Yun Chau Long Ben Loos Julia A Loos Manuela G López Guillermo López-Doménech José Antonio López-Guerrero Ana T López-Jiménez Óscar López-Pérez Israel López-Valero Magdalena J Lorenowicz Mar Lorente Peter Lorincz Laura Lossi Sophie Lotersztajn Penny E Lovat Jonathan F Lovell Alenka Lovy Péter Lőw Guang Lu Haocheng Lu Jia-Hong Lu Jin-Jian Lu Mengji Lu Shuyan Lu Alessandro Luciani John M Lucocq Paula Ludovico Micah A Luftig Morten Luhr Diego Luis-Ravelo Julian J Lum Liany Luna-Dulcey Anders H Lund Viktor K Lund Jan D Lünemann Patrick Lüningschrör Honglin Luo Rongcan Luo Shouqing Luo Zhi Luo Claudio Luparello Bernhard Lüscher Luan Luu Alex Lyakhovich Konstantin G Lyamzaev Alf Håkon Lystad Lyubomyr Lytvynchuk Alvin C Ma Changle Ma Mengxiao Ma Ning-Fang Ma Quan-Hong Ma Xinliang Ma Yueyun Ma Zhenyi Ma Ormond A MacDougald Fernando Macian Gustavo C MacIntosh Jeffrey P MacKeigan Kay F Macleod Sandra Maday Frank Madeo Muniswamy Madesh Tobias Madl Julio Madrigal-Matute Akiko Maeda Yasuhiro Maejima Marta Magarinos Poornima Mahavadi Emiliano Maiani Kenneth Maiese Panchanan Maiti Maria Chiara Maiuri Barbara Majello Michael B Major Elena Makareeva Fayaz Malik Karthik Mallilankaraman Walter Malorni Alina Maloyan Najiba Mammadova Gene Chi Wai Man Federico Manai Joseph D Mancias Eva-Maria Mandelkow Michael A Mandell Angelo A Manfredi Masoud H Manjili Ravi Manjithaya Patricio Manque Bella B Manshian Raquel Manzano Claudia Manzoni Kai Mao Cinzia Marchese Sandrine Marchetti Anna Maria Marconi Fabrizio Marcucci Stefania Mardente Olga A Mareninova Marta Margeta Muriel Mari Sara Marinelli Oliviero Marinelli Guillermo Mariño Sofia Mariotto Richard S Marshall Mark R Marten Sascha Martens Alexandre P J Martin Katie R Martin Sara Martin Shaun Martin Adrián Martín-Segura Miguel A Martín-Acebes Inmaculada Martin-Burriel Marcos Martin-Rincon Paloma Martin-Sanz José A Martina Wim Martinet Aitor Martinez Ana Martinez Jennifer Martinez Moises Martinez Velazquez Nuria Martinez-Lopez Marta Martinez-Vicente Daniel O Martins Joilson O Martins Waleska K Martins Tania Martins-Marques Emanuele Marzetti Shashank Masaldan Celine Masclaux-Daubresse Douglas G Mashek Valentina Massa Lourdes Massieu Glenn R Masson Laura Masuelli Anatoliy I Masyuk Tetyana V Masyuk Paola Matarrese Ander Matheu Satoaki Matoba Sachiko Matsuzaki Pamela Mattar Alessandro Matte Domenico Mattoscio José L Mauriz Mario Mauthe Caroline Mauvezin Emanual Maverakis Paola Maycotte Johanna Mayer Gianluigi Mazzoccoli Cristina Mazzoni Joseph R Mazzulli Nami McCarty Christine McDonald Mitchell R McGill Sharon L McKenna BethAnn McLaughlin Fionn McLoughlin Mark A McNiven Thomas G McWilliams Fatima Mechta-Grigoriou Tania Catarina Medeiros Diego L Medina Lynn A Megeney Klara Megyeri Maryam Mehrpour Jawahar L Mehta Alfred J Meijer Annemarie H Meijer Jakob Mejlvang Alicia Meléndez Annette Melk Gonen Memisoglu Alexandrina F Mendes Delong Meng Fei Meng Tian Meng Rubem Menna-Barreto Manoj B Menon Carol Mercer Anne E Mercier Jean-Louis Mergny Adalberto Merighi Seth D Merkley Giuseppe Merla Volker Meske Ana Cecilia Mestre Shree Padma Metur Christian Meyer Hemmo Meyer Wenyi Mi Jeanne Mialet-Perez Junying Miao Lucia Micale Yasuo Miki Enrico Milan Małgorzata Milczarek Dana L Miller Samuel I Miller Silke Miller Steven W Millward Ira Milosevic Elena A Minina Hamed Mirzaei Hamid Reza Mirzaei Mehdi Mirzaei Amit Mishra Nandita Mishra Paras Kumar Mishra Maja Misirkic Marjanovic Roberta Misasi Amit Misra Gabriella Misso Claire Mitchell Geraldine Mitou Tetsuji Miura Shigeki Miyamoto Makoto Miyazaki Mitsunori Miyazaki Taiga Miyazaki Keisuke Miyazawa Noboru Mizushima Trine H Mogensen Baharia Mograbi Reza Mohammadinejad Yasir Mohamud Abhishek Mohanty Sipra Mohapatra Torsten Möhlmann Asif Mohmmed Anna Moles Kelle H Moley Maurizio Molinari Vincenzo Mollace Andreas Buch Møller Bertrand Mollereau Faustino Mollinedo Costanza Montagna Mervyn J Monteiro Andrea Montella L Ruth Montes Barbara Montico Vinod K Mony Giacomo Monzio Compagnoni Michael N Moore Mohammad A Moosavi Ana L Mora Marina Mora David Morales-Alamo Rosario Moratalla Paula I Moreira Elena Morelli Sandra Moreno Daniel Moreno-Blas Viviana Moresi Benjamin Morga Alwena H Morgan Fabrice Morin Hideaki Morishita Orson L Moritz Mariko Moriyama Yuji Moriyasu Manuela Morleo Eugenia Morselli Jose F Moruno-Manchon Jorge Moscat Serge Mostowy Elisa Motori Andrea Felinto Moura Naima Moustaid-Moussa Maria Mrakovcic Gabriel Muciño-Hernández Anupam Mukherjee Subhadip Mukhopadhyay Jean M Mulcahy Levy Victoriano Mulero Sylviane Muller Christian Münch Ashok Munjal Pura Munoz-Canoves Teresa Muñoz-Galdeano Christian Münz Tomokazu Murakawa Claudia Muratori Brona M Murphy J Patrick Murphy Aditya Murthy Timo T Myöhänen Indira U Mysorekar Jennifer Mytych Seyed Mohammad Nabavi Massimo Nabissi Péter Nagy Jihoon Nah Aimable Nahimana Ichiro Nakagawa Ken Nakamura Hitoshi Nakatogawa Shyam S Nandi Meera Nanjundan Monica Nanni Gennaro Napolitano Roberta Nardacci Masashi Narita Melissa Nassif Ilana Nathan Manabu Natsumeda Ryno J Naude Christin Naumann Olaia Naveiras Fatemeh Navid Steffan T Nawrocki Taras Y Nazarko Francesca Nazio Florentina Negoita Thomas Neill Amanda L Neisch Luca M Neri Mihai G Netea Patrick Neubert Thomas P Neufeld Dietbert Neumann Albert Neutzner Phillip T Newton Paul A Ney Ioannis P Nezis Charlene C W Ng Tzi Bun Ng Hang T T Nguyen Long T Nguyen Hong-Min Ni Clíona Ní Cheallaigh Zhenhong Ni M Celeste Nicolao Francesco Nicoli Manuel Nieto-Diaz Per Nilsson Shunbin Ning Rituraj Niranjan Hiroshi Nishimune Mireia Niso-Santano Ralph A Nixon Annalisa Nobili Clevio Nobrega Takeshi Noda Uxía Nogueira-Recalde Trevor M Nolan Ivan Nombela Ivana Novak Beatriz Novoa Takashi Nozawa Nobuyuki Nukina Carmen Nussbaum-Krammer Jesper Nylandsted Tracey R O'Donovan Seónadh M O'Leary Eyleen J O'Rourke Mary P O'Sullivan Timothy E O'Sullivan Salvatore Oddo Ina Oehme Michinaga Ogawa Eric Ogier-Denis Margret H Ogmundsdottir Besim Ogretmen Goo Taeg Oh Seon-Hee Oh Young J Oh Takashi Ohama Yohei Ohashi Masaki Ohmuraya Vasileios Oikonomou Rani Ojha Koji Okamoto Hitoshi Okazawa Masahide Oku Sara Oliván Jorge M A Oliveira Michael Ollmann James A Olzmann Shakib Omari M Bishr Omary Gizem Önal Martin Ondrej Sang-Bing Ong Sang-Ging Ong Anna Onnis Juan A Orellana Sara Orellana-Muñoz Maria Del Mar Ortega-Villaizan Xilma R Ortiz-Gonzalez Elena Ortona Heinz D Osiewacz Abdel-Hamid K Osman Rosario Osta Marisa S Otegui Kinya Otsu Christiane Ott Luisa Ottobrini Jing-Hsiung James Ou Tiago F Outeiro Inger Oynebraten Melek Ozturk Gilles Pagès Susanta Pahari Marta Pajares Utpal B Pajvani Rituraj Pal Simona Paladino Nicolas Pallet Michela Palmieri Giuseppe Palmisano Camilla Palumbo Francesco Pampaloni Lifeng Pan Qingjun Pan Wenliang Pan Xin Pan Ganna Panasyuk Rahul Pandey Udai B Pandey Vrajesh Pandya Francesco Paneni Shirley Y Pang Elisa Panzarini Daniela L Papademetrio Elena Papaleo Daniel Papinski Diana Papp Eun Chan Park Hwan Tae Park Ji-Man Park Jong-In Park Joon Tae Park Junsoo Park Sang Chul Park Sang-Youel Park Abraham H Parola Jan B Parys Adrien Pasquier Benoit Pasquier João F Passos Nunzia Pastore Hemal H Patel Daniel Patschan Sophie Pattingre Gustavo Pedraza-Alva Jose Pedraza-Chaverri Zully Pedrozo Gang Pei Jianming Pei Hadas Peled-Zehavi Joaquín M Pellegrini Joffrey Pelletier Miguel A Peñalva Di Peng Ying Peng Fabio Penna Maria Pennuto Francesca Pentimalli Cláudia Mf Pereira Gustavo J S Pereira Lilian C Pereira Luis Pereira de Almeida Nirma D Perera Ángel Pérez-Lara Ana B Perez-Oliva María Esther Pérez-Pérez Palsamy Periyasamy Andras Perl Cristiana Perrotta Ida Perrotta Richard G Pestell Morten Petersen Irina Petrache Goran Petrovski Thorsten Pfirrmann Astrid S Pfister Jennifer A Philips Huifeng Pi Anna Picca Alicia M Pickrell Sandy Picot Giovanna M Pierantoni Marina Pierdominici Philippe Pierre Valérie Pierrefite-Carle Karolina Pierzynowska Federico Pietrocola Miroslawa Pietruczuk Claudio Pignata Felipe X Pimentel-Muiños Mario Pinar Roberta O Pinheiro Ronit Pinkas-Kramarski Paolo Pinton Karolina Pircs Sujan Piya Paola Pizzo Theo S Plantinga Harald W Platta Ainhoa Plaza-Zabala Markus Plomann Egor Y Plotnikov Helene Plun-Favreau Ryszard Pluta Roger Pocock Stefanie Pöggeler Christian Pohl Marc Poirot Angelo Poletti Marisa Ponpuak Hana Popelka Blagovesta Popova Helena Porta Soledad Porte Alcon Eliana Portilla-Fernandez Martin Post Malia B Potts Joanna Poulton Ted Powers Veena Prahlad Tomasz K Prajsnar Domenico Praticò Rosaria Prencipe Muriel Priault Tassula Proikas-Cezanne Vasilis J Promponas Christopher G Proud Rosa Puertollano Luigi Puglielli Thomas Pulinilkunnil Deepika Puri Rajat Puri Julien Puyal Xiaopeng Qi Yongmei Qi Wenbin Qian Lei Qiang Yu Qiu Joe Quadrilatero Jorge Quarleri Nina Raben Hannah Rabinowich Debora Ragona Michael J Ragusa Nader Rahimi Marveh Rahmati Valeria Raia Nuno Raimundo Namakkal-Soorappan Rajasekaran Sriganesh Ramachandra Rao Abdelhaq Rami Ignacio Ramírez-Pardo David B Ramsden Felix Randow Pundi N Rangarajan Danilo Ranieri Hai Rao Lang Rao Rekha Rao Sumit Rathore J Arjuna Ratnayaka Edward A Ratovitski Palaniyandi Ravanan Gloria Ravegnini Swapan K Ray Babak Razani Vito Rebecca Fulvio Reggiori Anne Régnier-Vigouroux Andreas S Reichert David Reigada Jan H Reiling Theo Rein Siegfried Reipert Rokeya Sultana Rekha Hongmei Ren Jun Ren Weichao Ren Tristan Renault Giorgia Renga Karen Reue Kim Rewitz Bruna Ribeiro de Andrade Ramos S Amer Riazuddin Teresa M Ribeiro-Rodrigues Jean-Ehrland Ricci Romeo Ricci Victoria Riccio Des R Richardson Yasuko Rikihisa Makarand V Risbud Ruth M Risueño Konstantinos Ritis Salvatore Rizza Rosario Rizzuto Helen C Roberts Luke D Roberts Katherine J Robinson Maria Carmela Roccheri Stephane Rocchi George G Rodney Tiago Rodrigues Vagner Ramon Rodrigues Silva Amaia Rodriguez Ruth Rodriguez-Barrueco Nieves Rodriguez-Henche Humberto Rodriguez-Rocha Jeroen Roelofs Robert S Rogers Vladimir V Rogov Ana I Rojo Krzysztof Rolka Vanina Romanello Luigina Romani Alessandra Romano Patricia S Romano David Romeo-Guitart Luis C Romero Montserrat Romero Joseph C Roney Christopher Rongo Sante Roperto Mathias T Rosenfeldt Philip Rosenstiel Anne G Rosenwald Kevin A Roth Lynn Roth Steven Roth Kasper M A Rouschop Benoit D Roussel Sophie Roux Patrizia Rovere-Querini Ajit Roy Aurore Rozieres Diego Ruano David C Rubinsztein Maria P Rubtsova Klaus Ruckdeschel Christoph Ruckenstuhl Emil Rudolf Rüdiger Rudolf Alessandra Ruggieri Avnika Ashok Ruparelia Paola Rusmini Ryan R Russell Gian Luigi Russo Maria Russo Rossella Russo Oxana O Ryabaya Kevin M Ryan Kwon-Yul Ryu Maria Sabater-Arcis Ulka Sachdev Michael Sacher Carsten Sachse Abhishek Sadhu Junichi Sadoshima Nathaniel Safren Paul Saftig Antonia P Sagona Gaurav Sahay Amirhossein Sahebkar Mustafa Sahin Ozgur Sahin Sumit Sahni Nayuta Saito Shigeru Saito Tsunenori Saito Ryohei Sakai Yasuyoshi Sakai Jun-Ichi Sakamaki Kalle Saksela Gloria Salazar Anna Salazar-Degracia Ghasem H Salekdeh Ashok K Saluja Belém Sampaio-Marques Maria Cecilia Sanchez Jose A Sanchez-Alcazar Victoria Sanchez-Vera Vanessa Sancho-Shimizu J Thomas Sanderson Marco Sandri Stefano Santaguida Laura Santambrogio Magda M Santana Giorgio Santoni Alberto Sanz Pascual Sanz Shweta Saran Marco Sardiello Timothy J Sargeant Apurva Sarin Chinmoy Sarkar Sovan Sarkar Maria-Rosa Sarrias Surajit Sarkar Dipanka Tanu Sarmah Jaakko Sarparanta Aishwarya Sathyanarayan Ranganayaki Sathyanarayanan K Matthew Scaglione Francesca Scatozza Liliana Schaefer Zachary T Schafer Ulrich E Schaible Anthony H V Schapira Michael Scharl Hermann M Schatzl Catherine H Schein Wiep Scheper David Scheuring Maria Vittoria Schiaffino Monica Schiappacassi Rainer Schindl Uwe Schlattner Oliver Schmidt Roland Schmitt Stephen D Schmidt Ingo Schmitz Eran Schmukler Anja Schneider Bianca E Schneider Romana Schober Alejandra C Schoijet Micah B Schott Michael Schramm Bernd Schröder Kai Schuh Christoph Schüller Ryan J Schulze Lea Schürmanns Jens C Schwamborn Melanie Schwarten Filippo Scialo Sebastiano Sciarretta Melanie J Scott Kathleen W Scotto A Ivana Scovassi Andrea Scrima Aurora Scrivo David Sebastian Salwa Sebti Simon Sedej Laura Segatori Nava Segev Per O Seglen Iban Seiliez Ekihiro Seki Scott B Selleck Frank W Sellke Joshua T Selsby Michael Sendtner Serif Senturk Elena Seranova Consolato Sergi Ruth Serra-Moreno Hiromi Sesaki Carmine Settembre Subba Rao Gangi Setty Gianluca Sgarbi Ou Sha John J Shacka Javeed A Shah Dantong Shang Changshun Shao Feng Shao Soroush Sharbati Lisa M Sharkey Dipali Sharma Gaurav Sharma Kulbhushan Sharma Pawan Sharma Surendra Sharma Han-Ming Shen Hongtao Shen Jiangang Shen Ming Shen Weili Shen Zheni Shen Rui Sheng Zhi Sheng Zu-Hang Sheng Jianjian Shi Xiaobing Shi Ying-Hong Shi Kahori Shiba-Fukushima Jeng-Jer Shieh Yohta Shimada Shigeomi Shimizu Makoto Shimozawa Takahiro Shintani Christopher J Shoemaker Shahla Shojaei Ikuo Shoji Bhupendra V Shravage Viji Shridhar Chih-Wen Shu Hong-Bing Shu Ke Shui Arvind K Shukla Timothy E Shutt Valentina Sica Aleem Siddiqui Amanda Sierra Virginia Sierra-Torre Santiago Signorelli Payel Sil Bruno J de Andrade Silva Johnatas D Silva Eduardo Silva-Pavez Sandrine Silvente-Poirot Rachel E Simmonds Anna Katharina Simon Hans-Uwe Simon Matias Simons Anurag Singh Lalit P Singh Rajat Singh Shivendra V Singh Shrawan K Singh Sudha B Singh Sunaina Singh Surinder Pal Singh Debasish Sinha Rohit Anthony Sinha Sangita Sinha Agnieszka Sirko Kapil Sirohi Efthimios L Sivridis Panagiotis Skendros Aleksandra Skirycz Iva Slaninová Soraya S Smaili Andrei Smertenko Matthew D Smith Stefaan J Soenen Eun Jung Sohn Sophia P M Sok Giancarlo Solaini Thierry Soldati Scott A Soleimanpour Rosa M Soler Alexei Solovchenko Jason A Somarelli Avinash Sonawane Fuyong Song Hyun Kyu Song Ju-Xian Song Kunhua Song Zhiyin Song Leandro R Soria Maurizio Sorice Alexander A Soukas Sandra-Fausia Soukup Diana Sousa Nadia Sousa Paul A Spagnuolo Stephen A Spector M M Srinivas Bharath Daret St Clair Venturina Stagni Leopoldo Staiano Clint A Stalnecker Metodi V Stankov Peter B Stathopulos Katja Stefan Sven Marcel Stefan Leonidas Stefanis Joan S Steffan Alexander Steinkasserer Harald Stenmark Jared Sterneckert Craig Stevens Veronika Stoka Stephan Storch Björn Stork Flavie Strappazzon Anne Marie Strohecker Dwayne G Stupack Huanxing Su Ling-Yan Su Longxiang Su Ana M Suarez-Fontes Carlos S Subauste Selvakumar Subbian Paula V Subirada Ganapasam Sudhandiran Carolyn M Sue Xinbing Sui Corey Summers Guangchao Sun Jun Sun Kang Sun Meng-Xiang Sun Qiming Sun Yi Sun Zhongjie Sun Karen K S Sunahara Eva Sundberg Katalin Susztak Peter Sutovsky Hidekazu Suzuki Gary Sweeney J David Symons Stephen Cho Wing Sze Nathaniel J Szewczyk Anna Tabęcka-Łonczynska Claudio Tabolacci Frank Tacke Heinrich Taegtmeyer Marco Tafani Mitsuo Tagaya Haoran Tai Stephen W G Tait Yoshinori Takahashi Szabolcs Takats Priti Talwar Chit Tam Shing Yau Tam Davide Tampellini Atsushi Tamura Chong Teik Tan Eng-King Tan Ya-Qin Tan Masaki Tanaka Motomasa Tanaka Daolin Tang Jingfeng Tang Tie-Shan Tang Isei Tanida Zhipeng Tao Mohammed Taouis Lars Tatenhorst Nektarios Tavernarakis Allen Taylor Gregory A Taylor Joan M Taylor Elena Tchetina Andrew R Tee Irmgard Tegeder David Teis Natercia Teixeira Fatima Teixeira-Clerc Kumsal A Tekirdag Tewin Tencomnao Sandra Tenreiro Alexei V Tepikin Pilar S Testillano Gianluca Tettamanti Pierre-Louis Tharaux Kathrin Thedieck Arvind A Thekkinghat Stefano Thellung Josephine W Thinwa V P Thirumalaikumar Sufi Mary Thomas Paul G Thomes Andrew Thorburn Lipi Thukral Thomas Thum Michael Thumm Ling Tian Ales Tichy Andreas Till Vincent Timmerman Vladimir I Titorenko Sokol V Todi Krassimira Todorova Janne M Toivonen Luana Tomaipitinca Dhanendra Tomar Cristina Tomas-Zapico Sergej Tomić Benjamin Chun-Kit Tong Chao Tong Xin Tong Sharon A Tooze Maria L Torgersen Satoru Torii Liliana Torres-López Alicia Torriglia Christina G Towers Roberto Towns Shinya Toyokuni Vladimir Trajkovic Donatella Tramontano Quynh-Giao Tran Leonardo H Travassos Charles B Trelford Shirley Tremel Ioannis P Trougakos Betty P Tsao Mario P Tschan Hung-Fat Tse Tak Fu Tse Hitoshi Tsugawa Andrey S Tsvetkov David A Tumbarello Yasin Tumtas María J Tuñón Sandra Turcotte Boris Turk Vito Turk Bradley J Turner Richard I Tuxworth Jessica K Tyler Elena V Tyutereva Yasuo Uchiyama Aslihan Ugun-Klusek Holm H Uhlig Marzena Ułamek-Kozioł Ilya V Ulasov Midori Umekawa Christian Ungermann Rei Unno Sylvie Urbe Elisabet Uribe-Carretero Suayib Üstün Vladimir N Uversky Thomas Vaccari Maria I Vaccaro Björn F Vahsen Helin Vakifahmetoglu-Norberg Rut Valdor Maria J Valente Ayelén Valko Richard B Vallee Angela M Valverde Greet Van den Berghe Stijn van der Veen Luc Van Kaer Jorg van Loosdregt Sjoerd J L van Wijk Wim Vandenberghe Ilse Vanhorebeek Marcos A Vannier-Santos Nicola Vannini M Cristina Vanrell Chiara Vantaggiato Gabriele Varano Isabel Varela-Nieto Máté Varga M Helena Vasconcelos Somya Vats Demetrios G Vavvas Ignacio Vega-Naredo Silvia Vega-Rubin-de-Celis Guillermo Velasco Ariadna P Velázquez Tibor Vellai Edo Vellenga Francesca Velotti Mireille Verdier Panayotis Verginis Isabelle Vergne Paul Verkade Manish Verma Patrik Verstreken Tim Vervliet Jörg Vervoorts Alexandre T Vessoni Victor M Victor Michel Vidal Chiara Vidoni Otilia V Vieira Richard D Vierstra Sonia Viganó Helena Vihinen Vinoy Vijayan Miquel Vila Marçal Vilar José M Villalba Antonio Villalobo Beatriz Villarejo-Zori Francesc Villarroya Joan Villarroya Olivier Vincent Cecile Vindis Christophe Viret Maria Teresa Viscomi Dora Visnjic Ilio Vitale David J Vocadlo Olga V Voitsekhovskaja Cinzia Volonté Mattia Volta Marta Vomero Clarissa Von Haefen Marc A Vooijs Wolfgang Voos Ljubica Vucicevic Richard Wade-Martins Satoshi Waguri Kenrick A Waite Shuji Wakatsuki David W Walker Mark J Walker Simon A Walker Jochen Walter Francisco G Wandosell Bo Wang Chao-Yung Wang Chen Wang Chenran Wang Chenwei Wang Cun-Yu Wang Dong Wang Fangyang Wang Feng Wang Fengming Wang Guansong Wang Han Wang Hao Wang Hexiang Wang Hong-Gang Wang Jianrong Wang Jigang Wang Jiou Wang Jundong Wang Kui Wang Lianrong Wang Liming Wang Maggie Haitian Wang Meiqing Wang Nanbu Wang Pengwei Wang Peipei Wang Ping Wang Ping Wang Qing Jun Wang Qing Wang Qing Kenneth Wang Qiong A Wang Wen-Tao Wang Wuyang Wang Xinnan Wang Xuejun Wang Yan Wang Yanchang Wang Yanzhuang Wang Yen-Yun Wang Yihua Wang Yipeng Wang Yu Wang Yuqi Wang Zhe Wang Zhenyu Wang Zhouguang Wang Gary Warnes Verena Warnsmann Hirotaka Watada Eizo Watanabe Maxinne Watchon Anna Wawrzyńska Timothy E Weaver Grzegorz Wegrzyn Ann M Wehman Huafeng Wei Lei Wei Taotao Wei Yongjie Wei Oliver H Weiergräber Conrad C Weihl Günther Weindl Ralf Weiskirchen Alan Wells Runxia H Wen Xin Wen Antonia Werner Beatrice Weykopf Sally P Wheatley J Lindsay Whitton Alexander J Whitworth Katarzyna Wiktorska Manon E Wildenberg Tom Wileman Simon Wilkinson Dieter Willbold Brett Williams Robin S B Williams Roger L Williams Peter R Williamson Richard A Wilson Beate Winner Nathaniel J Winsor Steven S Witkin Harald Wodrich Ute Woehlbier Thomas Wollert Esther Wong Jack Ho Wong Richard W Wong Vincent Kam Wai Wong W Wei-Lynn Wong An-Guo Wu Chengbiao Wu Jian Wu Junfang Wu Kenneth K Wu Min Wu Shan-Ying Wu Shengzhou Wu Shu-Yan Wu Shufang Wu William K K Wu Xiaohong Wu Xiaoqing Wu Yao-Wen Wu Yihua Wu Ramnik J Xavier Hongguang Xia Lixin Xia Zhengyuan Xia Ge Xiang Jin Xiang Mingliang Xiang Wei Xiang Bin Xiao Guozhi Xiao Hengyi Xiao Hong-Tao Xiao Jian Xiao Lan Xiao Shi Xiao Yin Xiao Baoming Xie Chuan-Ming Xie Min Xie Yuxiang Xie Zhiping Xie Zhonglin Xie Maria Xilouri Congfeng Xu En Xu Haoxing Xu Jing Xu JinRong Xu Liang Xu Wen Wen Xu Xiulong Xu Yu Xue Sokhna M S Yakhine-Diop Masamitsu Yamaguchi Osamu Yamaguchi Ai Yamamoto Shunhei Yamashina Shengmin Yan Shian-Jang Yan Zhen Yan Yasuo Yanagi Chuanbin Yang Dun-Sheng Yang Huan Yang Huang-Tian Yang Hui Yang Jin-Ming Yang Jing Yang Jingyu Yang Ling Yang Liu Yang Ming Yang Pei-Ming Yang Qian Yang Seungwon Yang Shu Yang Shun-Fa Yang Wannian Yang Wei Yuan Yang Xiaoyong Yang Xuesong Yang Yi Yang Ying Yang Honghong Yao Shenggen Yao Xiaoqiang Yao Yong-Gang Yao Yong-Ming Yao Takahiro Yasui Meysam Yazdankhah Paul M Yen Cong Yi Xiao-Ming Yin Yanhai Yin Zhangyuan Yin Ziyi Yin Meidan Ying Zheng Ying Calvin K Yip Stephanie Pei Tung Yiu Young H Yoo Kiyotsugu Yoshida Saori R Yoshii Tamotsu Yoshimori Bahman Yousefi Boxuan Yu Haiyang Yu Jun Yu Jun Yu Li Yu Ming-Lung Yu Seong-Woon Yu Victor C Yu W Haung Yu Zhengping Yu Zhou Yu Junying Yuan Ling-Qing Yuan Shilin Yuan Shyng-Shiou F Yuan Yanggang Yuan Zengqiang Yuan Jianbo Yue Zhenyu Yue Jeanho Yun Raymond L Yung David N Zacks Gabriele Zaffagnini Vanessa O Zambelli Isabella Zanella Qun S Zang Sara Zanivan Silvia Zappavigna Pilar Zaragoza Konstantinos S Zarbalis Amir Zarebkohan Amira Zarrouk Scott O Zeitlin Jialiu Zeng Ju-Deng Zeng Eva Žerovnik Lixuan Zhan Bin Zhang Donna D Zhang Hanlin Zhang Hong Zhang Hong Zhang Honghe Zhang Huafeng Zhang Huaye Zhang Hui Zhang Hui-Ling Zhang Jianbin Zhang Jianhua Zhang Jing-Pu Zhang Kalin Y B Zhang Leshuai W Zhang Lin Zhang Lisheng Zhang Lu Zhang Luoying Zhang Menghuan Zhang Peng Zhang Sheng Zhang Wei Zhang Xiangnan Zhang Xiao-Wei Zhang Xiaolei Zhang Xiaoyan Zhang Xin Zhang Xinxin Zhang Xu Dong Zhang Yang Zhang Yanjin Zhang Yi Zhang Ying-Dong Zhang Yingmei Zhang Yuan-Yuan Zhang Yuchen Zhang Zhe Zhang Zhengguang Zhang Zhibing Zhang Zhihai Zhang Zhiyong Zhang Zili Zhang Haobin Zhao Lei Zhao Shuang Zhao Tongbiao Zhao Xiao-Fan Zhao Ying Zhao Yongchao Zhao Yongliang Zhao Yuting Zhao Guoping Zheng Kai Zheng Ling Zheng Shizhong Zheng Xi-Long Zheng Yi Zheng Zu-Guo Zheng Boris Zhivotovsky Qing Zhong Ao Zhou Ben Zhou Cefan Zhou Gang Zhou Hao Zhou Hong Zhou Hongbo Zhou Jie Zhou Jing Zhou Jing Zhou Jiyong Zhou Kailiang Zhou Rongjia Zhou Xu-Jie Zhou Yanshuang Zhou Yinghong Zhou Yubin Zhou Zheng-Yu Zhou Zhou Zhou Binglin Zhu Changlian Zhu Guo-Qing Zhu Haining Zhu Hongxin Zhu Hua Zhu Wei-Guo Zhu Yanping Zhu Yushan Zhu Haixia Zhuang Xiaohong Zhuang Katarzyna Zientara-Rytter Christine M Zimmermann Elena Ziviani Teresa Zoladek Wei-Xing Zong Dmitry B Zorov Antonio Zorzano Weiping Zou Zhen Zou Zhengzhi Zou Steven Zuryn Werner Zwerschke Beate Brand-Saberi X Charlie Dong Chandra Shekar Kenchappa Zuguo Li Yong Lin Shigeru Oshima Yueguang Rong Judith C Sluimer Christina L Stallings Chun-Kit Tong

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

Hong Kong Baptist University, School of Chinese Medicine, Hong Kong, China.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

LATS1 but not LATS2 represses autophagy by a kinase-independent scaffold function.

Nat Commun 2019 12 17;10(1):5755. Epub 2019 Dec 17.

Department of Biomedicine, University of Basel, Basel, Switzerland.

Autophagy perturbation represents an emerging therapeutic strategy in cancer. Although LATS1 and LATS2 kinases, core components of the mammalian Hippo pathway, have been shown to exert tumor suppressive activities, here we report a pro-survival role of LATS1 but not LATS2 in hepatocellular carcinoma (HCC) cells. Specifically, LATS1 restricts lethal autophagy in HCC cells induced by sorafenib, the standard of care for advanced HCC patients. Notably, autophagy regulation by LATS1 is independent of its kinase activity. Instead, LATS1 stabilizes the autophagy core-machinery component Beclin-1 by promoting K27-linked ubiquitination at lysine residues K32 and K263 on Beclin-1. Consequently, ubiquitination of Beclin-1 negatively regulates autophagy by promoting inactive dimer formation of Beclin-1. Our study highlights a functional diversity between LATS1 and LATS2, and uncovers a scaffolding role of LATS1 in mediating a cross-talk between the Hippo signaling pathway and autophagy.
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http://dx.doi.org/10.1038/s41467-019-13591-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917744PMC
December 2019

STK38 kinase acts as XPO1 gatekeeper regulating the nuclear export of autophagy proteins and other cargoes.

EMBO Rep 2019 11 23;20(11):e48150. Epub 2019 Sep 23.

ART Group, Inserm U830, Paris, France.

STK38 (also known as NDR1) is a Hippo pathway serine/threonine protein kinase with multifarious functions in normal and cancer cells. Using a context-dependent proximity-labeling assay, we identify more than 250 partners of STK38 and find that STK38 modulates its partnership depending on the cellular context by increasing its association with cytoplasmic proteins upon nutrient starvation-induced autophagy and with nuclear ones during ECM detachment. We show that STK38 shuttles between the nucleus and the cytoplasm and that its nuclear exit depends on both XPO1 (aka exportin-1, CRM1) and STK38 kinase activity. We further uncover that STK38 modulates XPO1 export activity by phosphorylating XPO1 on serine 1055, thus regulating its own nuclear exit. We expand our model to other cellular contexts by discovering that XPO1 phosphorylation by STK38 regulates also the nuclear exit of Beclin1 and YAP1, key regulator of autophagy and transcriptional effector, respectively. Collectively, our results reveal STK38 as an activator of XPO1, behaving as a gatekeeper of nuclear export. These observations establish a novel mechanism of XPO1-dependent cargo export regulation by phosphorylation of XPO1's C-terminal auto-inhibitory domain.
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http://dx.doi.org/10.15252/embr.201948150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832005PMC
November 2019

The Hippo network kinase STK38 contributes to protein homeostasis by inhibiting BAG3-mediated autophagy.

Biochim Biophys Acta Mol Cell Res 2019 10 19;1866(10):1556-1566. Epub 2019 Jul 19.

Institute for Cell Biology, University of Bonn, Ulrich-Haberland-Str. 61a, 53121 Bonn, Germany. Electronic address:

Chaperone-assisted selective autophagy (CASA) initiated by the cochaperone Bcl2-associated athanogene 3 (BAG3) represents an important mechanism for the disposal of misfolded and damaged proteins in mammalian cells. Under mechanical stress, the cochaperone cooperates with the small heat shock protein HSPB8 and the cytoskeleton-associated protein SYNPO2 to degrade force-unfolded forms of the actin-crosslinking protein filamin. This is essential for muscle maintenance in flies, fish, mice and men. Here, we identify the serine/threonine protein kinase 38 (STK38), which is part of the Hippo signaling network, as a novel interactor of BAG3. STK38 was previously shown to facilitate cytoskeleton assembly and to promote mitophagy as well as starvation and detachment induced autophagy. Significantly, our study reveals that STK38 exerts an inhibitory activity on BAG3-mediated autophagy. Inhibition relies on a disruption of the functional interplay of BAG3 with HSPB8 and SYNPO2 upon binding of STK38 to the cochaperone. Of note, STK38 attenuates CASA independently of its kinase activity, whereas previously established regulatory functions of STK38 involve target phosphorylation. The ability to exert different modes of regulation on central protein homeostasis (proteostasis) machineries apparently allows STK38 to coordinate the execution of diverse macroautophagy pathways and to balance cytoskeleton assembly and degradation.
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http://dx.doi.org/10.1016/j.bbamcr.2019.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692498PMC
October 2019

MOB (Mps one Binder) Proteins in the Hippo Pathway and Cancer.

Cells 2019 06 10;8(6). Epub 2019 Jun 10.

UCL Cancer Institute, University College London, WC1E 6BT, London, United Kingdom.

The family of MOBs (monopolar spindle-one-binder proteins) is highly conserved in the eukaryotic kingdom. MOBs represent globular scaffold proteins without any known enzymatic activities. They can act as signal transducers in essential intracellular pathways. MOBs have diverse cancer-associated cellular functions through regulatory interactions with members of the NDR/LATS kinase family. By forming additional complexes with serine/threonine protein kinases of the germinal centre kinase families, other enzymes and scaffolding factors, MOBs appear to be linked to an even broader disease spectrum. Here, we review our current understanding of this emerging protein family, with emphases on post-translational modifications, protein-protein interactions, and cellular processes that are possibly linked to cancer and other diseases. In particular, we summarise the roles of MOBs as core components of the Hippo tissue growth and regeneration pathway.
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http://dx.doi.org/10.3390/cells8060569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627106PMC
June 2019

NDR2 kinase contributes to cell invasion and cytokinesis defects induced by the inactivation of RASSF1A tumor-suppressor gene in lung cancer cells.

J Exp Clin Cancer Res 2019 Apr 12;38(1):158. Epub 2019 Apr 12.

Normandie University, UNICAEN, CEA, CNRS, ISTCT/CERVOxy group, GIP CYCERON, Avenue H.Becquerel- 14074, F-14000, Caen, France.

Background: RASSF1A, a tumor suppressor gene, is frequently inactivated in lung cancer leading to a YAP-dependent epithelial-mesenchymal transition (EMT). Such effects are partly due to the inactivation of the anti-migratory RhoB GTPase via the inhibitory phosphorylation of GEF-H1, the GDP/GTP exchange factor for RhoB. However, the kinase responsible for RhoB/GEF-H1 inactivation in RASSF1A-depleted cells remained unknown.

Methods: NDR1/2 inactivation by siRNA or shRNA effects on epithelial-mesenchymal transition, invasion, xenograft formation and growth in SCID-/- Beige mice, apoptosis, proliferation, cytokinesis, YAP/TAZ activation were investigated upon RASSF1A loss in human bronchial epithelial cells (HBEC).

Results: We demonstrate here that depletion of the YAP-kinases NDR1/2 reverts migration and metastatic properties upon RASSF1A loss in HBEC. We show that NDR2 interacts directly with GEF-H1 (which contains the NDR phosphorylation consensus motif HXRXXS/T), leading to GEF-H1 phosphorylation. We further report that the RASSF1A/NDR2/GEF-H1/RhoB/YAP axis is involved in proper cytokinesis in human bronchial cells, since chromosome proper segregation are NDR-dependent upon RASSF1A or GEF-H1 loss in HBEC.

Conclusion: To summarize, our data support a model in which, upon RASSF1A silencing, NDR2 gets activated, phosphorylates and inactivates GEF-H1, leading to RhoB inactivation. This cascade induced by RASSF1A loss in bronchial cells is responsible for metastasis properties, YAP activation and cytokinesis defects.
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http://dx.doi.org/10.1186/s13046-019-1145-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461807PMC
April 2019

MST1/2 Kinase Assays Using Recombinant Proteins.

Methods Mol Biol 2019 ;1893:319-331

Cancer Institute, University College London, London, UK.

The Hippo tumor suppressor pathway is fundamental to the coordination of death, growth, proliferation, and differentiation on the cellular level. At the molecular level, a highly conserved Hippo core cassette is central for the regulation of effector activities such as the co-transcriptional activity of YAP. In particular, the mammalian MST1/2 serine/threonine protein kinases (termed Hippo kinase in Drosophila melanogaster) can act as central signal transducers as part of the Hippo core cassette. In this chapter we describe in vitro kinase assays using recombinant MST1/2 kinases and recombinant MST1/2 kinase substrate.
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http://dx.doi.org/10.1007/978-1-4939-8910-2_24DOI Listing
June 2019

Measuring the Kinase Activities of the LATS/NDR Protein Kinases.

Methods Mol Biol 2019 ;1893:305-317

Cancer Institute, University College London, London, UK.

The Hippo tissue growth control and regeneration pathway is a main regulator of the YAP/TAZ effectors. In this regard, the LATS/NDR serine/threonine protein kinases can function as central components of the Hippo core module. More specifically, LATS/NDR-mediated phosphorylation of YAP/TAZ on different residues can regulate the subcellular localization and/or stability of YAP/TAZ. Therefore, the assessment of LATS/NDR activities can serve as readout for the activity status of the Hippo pathway. Here, we describe our preferred methodology regarding the measurement of the activities of LATS/NDR kinases.
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http://dx.doi.org/10.1007/978-1-4939-8910-2_23DOI Listing
June 2019

A Hippo-like Signaling Pathway Controls Tracheal Morphogenesis in Drosophila melanogaster.

Dev Cell 2018 12 25;47(5):564-575.e5. Epub 2018 Oct 25.

Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3010, Australia; Department of Pathology, University of Melbourne, Parkville, VIC 3010, Australia; Department of Anatomy and Developmental Biology and Biomedicine Discovery Institute, Monash University, Clayton, VIC 3168, Australia. Electronic address:

Hippo-like pathways are ancient signaling modules first identified in yeasts. The best-defined metazoan module forms the core of the Hippo pathway, which regulates organ size and cell fate. Hippo-like kinase modules consist of a Sterile 20-like kinase, an NDR kinase, and non-catalytic protein scaffolds. In the Hippo pathway, the upstream kinase Hippo can be activated by another kinase, Tao-1. Here, we delineate a related Hippo-like signaling module that Tao-1 regulates to control tracheal morphogenesis in Drosophila melanogaster. Tao-1 activates the Sterile 20-like kinase GckIII by phosphorylating its activation loop, a mode of regulation that is conserved in humans. Tao-1 and GckIII act upstream of the NDR kinase Tricornered to ensure proper tube formation in trachea. Our study reveals that Tao-1 activates two related kinase modules to control both growth and morphogenesis. The Hippo-like signaling pathway we have delineated has a potential role in the human vascular disease cerebral cavernous malformation.
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http://dx.doi.org/10.1016/j.devcel.2018.09.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281297PMC
December 2018

STK38L kinase ablation promotes loss of cell viability in a subset of KRAS-dependent pancreatic cancer cell lines.

Oncotarget 2017 Oct 11;8(45):78556-78572. Epub 2017 Sep 11.

Department of Pharmacology and Experimental Therapeutics, Center for Cancer Research, Boston University Graduate School of Medicine, Boston, MA, USA.

Pancreatic ductal adenocarcinomas (PDACs) are highly aggressive malignancies, associated with poor clinical prognosis and limited therapeutic options. Oncogenic mutations are found in over 90% of PDACs, playing a central role in tumor progression. Global gene expression profiling of PDAC reveals 3-4 major molecular subtypes with distinct phenotypic traits and pharmacological vulnerabilities, including variations in oncogenic KRAS pathway dependencies. PDAC cell lines of the aberrantly differentiated endocrine exocrine (ADEX) subtype are robustly KRAS-dependent for survival. The gene is located on chromosome 12p11-12p12, a region amplified in 5-10% of primary PDACs. Within this amplicon, we identified co-amplification of with the gene in a subset of primary human PDACs and PDAC cell lines. Therefore, we determined whether PDAC cell lines are dependent on expression for proliferation and viability. encodes a serine/threonine kinase, which shares homology with Hippo pathway kinases LATS1/2. We show that expression is elevated in a subset of primary PDACs and PDAC cell lines displaying ADEX subtype characteristics, including overexpression of mutant KRAS. RNAi-mediated depletion of STK38L in a subset of ADEX subtype cell lines inhibits cellular proliferation and induces apoptosis. Concomitant with these effects, STK38L depletion causes increased expression of the LATS2 kinase and the cell cycle regulator p21. LATS2 depletion partially rescues the cytostatic and cytotoxic effects of STK38L depletion. Lastly, high mRNA expression is associated with decreased overall patient survival in PDACs. Collectively, our findings implicate STK38L as a candidate targetable vulnerability in a subset of molecularly-defined PDACs.
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http://dx.doi.org/10.18632/oncotarget.20833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667982PMC
October 2017

Stable MOB1 interaction with Hippo/MST is not essential for development and tissue growth control.

Nat Commun 2017 09 25;8(1):695. Epub 2017 Sep 25.

Tumour Suppressor Signalling Network Laboratory, UCL Cancer Institute, University College London, London, WC1E 6BT, UK.

The Hippo tumor suppressor pathway is essential for development and tissue growth control, encompassing a core cassette consisting of the Hippo (MST1/2), Warts (LATS1/2), and Tricornered (NDR1/2) kinases together with MOB1 as an important signaling adaptor. However, it remains unclear which regulatory interactions between MOB1 and the different Hippo core kinases coordinate development, tissue growth, and tumor suppression. Here, we report the crystal structure of the MOB1/NDR2 complex and define key MOB1 residues mediating MOB1's differential binding to Hippo core kinases, thereby establishing MOB1 variants with selective loss-of-interaction. By studying these variants in human cancer cells and Drosophila, we uncovered that MOB1/Warts binding is essential for tumor suppression, tissue growth control, and development, while stable MOB1/Hippo binding is dispensable and MOB1/Trc binding alone is insufficient. Collectively, we decrypt molecularly, cell biologically, and genetically the importance of the diverse interactions of Hippo core kinases with the pivotal MOB1 signal transducer.The Hippo tumor suppressor pathway is essential for development and tissue growth control. Here the authors employ a multi-disciplinary approach to characterize the interactions of the three Hippo kinases with the signaling adaptor MOB1 and show how they differently affect development, tissue growth and tumor suppression.
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http://dx.doi.org/10.1038/s41467-017-00795-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612953PMC
September 2017

The NDR/LATS protein kinases in immunology and cancer biology.

Semin Cancer Biol 2018 02 1;48:104-114. Epub 2017 Jun 1.

Tumour Suppressor Signalling Networks Laboratory, UCL Cancer Institute, University College London, WC1E 6BT, London, United Kingdom. Electronic address:

The NDR (nuclear Dbf2-related)/LATS (large tumour suppressor) family of kinases represents a subclass of the AGC (protein kinase A (PKA)/PKG/PKC-like) group of serine/threonine protein kinases. Members of the NDR/LATS family are vital components of conserved pathways controlling essential cellular processes, such as proliferation (cell cycle progression) and cell death. In particular, the central involvement of NDR/LATS as YAP/TAZ kinases in the Hippo tissue growth control pathway has gained much interest. In this review, we summarise the roles of mammalian NDR1/2 (aka STK38/STK38L) and LATS1/2 in immunity and cancer biology. We also discuss the activation mechanisms of NDR/LATS involving Ste20-like kinases and the MOB1 signal transducer, followed by an overview of NDR/LATS knockout mouse models. We further review the mutation and expression status of NDR/LATS in human cancers and their possible predictive and/or prognostic value in cancer treatment.
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http://dx.doi.org/10.1016/j.semcancer.2017.04.010DOI Listing
February 2018

The promise of using histone deacetylase inhibitors in combination treatment against breast cancer and other solid tumors.

Chin Clin Oncol 2017 02 6;6(1). Epub 2017 Feb 6.

Tumour Suppressor Signalling Networks Laboratory, UCL Cancer Institute, University College London, London, UK.

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http://dx.doi.org/10.21037/cco.2017.01.05DOI Listing
February 2017

The Possible Crosstalk of MOB2 With NDR1/2 Kinases in Cell Cycle and DNA Damage Signaling.

J Cell Signal 2016 Sep;1:125

Tumour Suppressor Signaling Networks Laboratory, UCL Cancer Institute, University College London, UK.

This article is the authors' opinion of the roles of the signal transducer Mps one binder 2 (MOB2) in the control of cell cycle progression and the DNA Damage Response (DDR). We recently found that endogenous MOB2 is required to prevent the accumulation of endogenous DNA damage in order to prevent the undesired, and possibly detrimental, activation of cell cycle checkpoints. In this regard, it is noteworthy that MOB2 has been linked biochemically to the regulation of the NDR1/2 (aka STK38/STK38L) protein kinases, which themselves have functions at different steps of the cell cycle. Therefore, we are speculating in this article about the possible connections of MOB2 with NDR1/2 kinases in cell cycle and DDR Signaling.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321467PMC
September 2016

YAP needs Nemo to guide a Hippo.

EMBO Rep 2017 01 15;18(1):3-4. Epub 2016 Dec 15.

Tumour Suppressor Signalling Networks Laboratory, UCL Cancer Institute, University College London, London, UK.

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http://dx.doi.org/10.15252/embr.201643622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210086PMC
January 2017

Hippo Signaling in Mitosis: An Updated View in Light of the MEN Pathway.

Methods Mol Biol 2017 ;1505:265-277

Tumour Suppressor Signalling Networks Laboratory, UCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6BT, UK.

The Hippo pathway is an essential tumor suppressor signaling network that coordinates cell proliferation, death, and differentiation in higher eukaryotes. Intriguingly, the core components of the Hippo pathway are conserved from yeast to man, with the yeast analogs of mammalian MST1/2 (fly Hippo), MOB1 (fly Mats), LATS1/2 (fly Warts), and NDR1/2 (fly Tricornered) functioning as essential components of the mitotic exit network (MEN). Here, we update our previous summary of mitotic functions of Hippo core components in Drosophila melanogaster and mammals, with particular emphasis on similarities between the yeast MEN pathway and mitotic Hippo signaling. Mitotic functions of YAP and TAZ, the two main effectors of Hippo signaling, are also discussed.
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http://dx.doi.org/10.1007/978-1-4939-6502-1_19DOI Listing
January 2018

Platinum-Based Chemotherapy Induces Methylation Changes in Blood DNA Associated with Overall Survival in Patients with Ovarian Cancer.

Clin Cancer Res 2017 May 23;23(9):2213-2222. Epub 2016 Sep 23.

Department of Surgery and Cancer, Imperial College London, London, UK.

DNA damage repair can lead to epigenetic changes. DNA mismatch repair proteins bind to platinum DNA adducts and at sites of DNA damage can recruit the DNA methylating enzyme DNMT1, resulting in aberrant methylation. We hypothesised that DNA damage repair during platinum-based chemotherapy may cause aberrant DNA methylation in normal tissues of patients such as blood. We used Illumina 450k methylation arrays and bisulphite pyrosequencing to investigate methylation at presentation and relapse in blood DNA from patients with ovarian cancer enrolled in the SCOTROC1 trial ( = 247) and in a cohort of ovarian tumor DNA samples collected at first relapse ( = 46). We used an ovarian cancer cell line model to investigate the role of the DNA mismatch repair gene in platinum-induced methylation changes. Specific CpG methylation changes in blood at relapse are observed following platinum-based chemotherapy and are associated with patient survival, independent of other clinical factors [hazard ratio, 3.7; 95% confidence interval, 1.8-7.6, = 2.8 × 10]. Similar changes occur in ovarian tumors at relapse, also associated with patient survival (hazard ratio, 2.6; 95% confidence interval, 1.0-6.8, = 0.048). Using an ovarian cancer cell line model, we demonstrate that functional mismatch repair increases the frequency of platinum-induced methylation. DNA methylation in blood at relapse following chemotherapy, and not at presentation, is informative regarding survival of patients with ovarian cancer. Functional DNA mismatch repair increases the frequency of DNA methylation changes induced by platinum. DNA methylation in blood following chemotherapy could provide a noninvasive means of monitoring patients' epigenetic responses to treatment without requiring a tumor biopsy. .
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http://dx.doi.org/10.1158/1078-0432.CCR-16-1754DOI Listing
May 2017

Mitochondrial clearance by the STK38 kinase supports oncogenic Ras-induced cell transformation.

Oncotarget 2016 Jul;7(28):44142-44160

University College London, Cancer Institute, London, WC1E 6BT, United Kingdom.

Oncogenic Ras signalling occurs frequently in many human cancers. However, no effective targeted therapies are currently available to treat patients suffering from Ras-driven tumours. Therefore, it is imperative to identify downstream effectors of Ras signalling that potentially represent promising new therapeutic options. Particularly, considering that autophagy inhibition can impair the survival of Ras-transformed cells in tissue culture and mouse models, an understanding of factors regulating the balance between autophagy and apoptosis in Ras-transformed human cells is needed. Here, we report critical roles of the STK38 protein kinase in oncogenic Ras transformation. STK38 knockdown impaired anoikis resistance, anchorage-independent soft agar growth, and in vivo xenograft growth of Ras-transformed human cells. Mechanistically, STK38 supports Ras-driven transformation through promoting detachment-induced autophagy. Even more importantly, upon cell detachment STK38 is required to sustain the removal of damaged mitochondria by mitophagy, a selective autophagic process, to prevent excessive mitochondrial reactive oxygen species production that can negatively affect cancer cell survival. Significantly, knockdown of PINK1 or Parkin, two positive regulators of mitophagy, also impaired anoikis resistance and anchorage-independent growth of Ras-transformed human cells, while knockdown of USP30, a negative regulator of PINK1/Parkin-mediated mitophagy, restored anchorage-independent growth of STK38-depleted Ras-transformed human cells. Therefore, our findings collectively reveal novel molecular players that determine whether Ras-transformed human cells die or survive upon cell detachment, which potentially could be exploited for the development of novel strategies to target Ras-transformed cells.
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http://dx.doi.org/10.18632/oncotarget.9875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5190085PMC
July 2016

The Roles of NDR Protein Kinases in Hippo Signalling.

Genes (Basel) 2016 May 18;7(5). Epub 2016 May 18.

Cancer Institute, University College London, Paul O'Gorman building, 72 Huntley Street, London WC1E 6BT, UK.

The Hippo tumour suppressor pathway has emerged as a critical regulator of tissue growth through controlling cellular processes such as cell proliferation, death, differentiation and stemness. Traditionally, the core cassette of the Hippo pathway includes the MST1/2 protein kinases, the LATS1/2 protein kinases, and the MOB1 scaffold signal transducer, which together regulate the transcriptional co-activator functions of the proto-oncoproteins YAP and TAZ through LATS1/2-mediated phosphorylation of YAP/TAZ. Recent research has identified additional kinases, such as NDR1/2 (also known as STK38/STK38L) and MAP4Ks, which should be considered as novel members of the Hippo core cassette. While these efforts helped to expand our understanding of Hippo core signalling, they also began to provide insights into the complexity and redundancy of the Hippo signalling network. Here, we focus on summarising our current knowledge of the regulation and functions of mammalian NDR kinases, discussing parallels between the NDR pathways in Drosophila and mammals. Initially, we provide a general overview of the cellular functions of NDR kinases in cell cycle progression, centrosome biology, apoptosis, autophagy, DNA damage signalling, immunology and neurobiology. Finally, we put particular emphasis on discussing NDR1/2 as YAP kinases downstream of MST1/2 and MOB1 signalling in Hippo signalling.
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http://dx.doi.org/10.3390/genes7050021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880841PMC
May 2016

The characterisation of LATS2 kinase regulation in Hippo-YAP signalling.

Cell Signal 2016 May 18;28(5):488-497. Epub 2016 Feb 18.

Tumour Suppressor Signalling Network Laboratory, UCL Cancer Institute, University College London, WC1E 6BT London, United Kingdom. Electronic address:

By controlling the YAP1 proto-oncoprotein Hippo signalling plays important roles in cancer-associated processes. Current evidence suggests that the Hippo kinases MST1/2 together with the MOB1 scaffold protein promote the formation of active MOB1/LATS complexes which phosphorylate and thereby inhibit YAP1. However, the regulatory mechanisms of MST1/2-MOB1-LATS signalling are currently underinvestigated. Therefore, we studied LATS2 variants carrying specific modifications that mimic gain or loss of phosphorylation and/or abolish MOB1/LATS2 interactions. We discovered that Ser872 T-loop and Thr1041 hydrophobic motif (HM) phosphorylation of LATS2 is essential for LATS2 activation. MST1/2 phosphorylate LATS2 on Thr1041, but not Ser872, while MOB1 binding to LATS2 supports both phosphorylation events. Significantly, LATS2-PIF, a LATS2 variant containing the PRK2 HM, acts as a hyperactive LATS2 kinase that efficiently phosphorylates YAP1 and inhibits the transcriptional co-activity of YAP1. This inhibitory function of LATS2-PIF is dependent on LATS2 kinase activity, while MOB1/LATS2 and YAP1/LATS2 complex formation is dispensable, suggesting that elevated LATS2 kinase activity can be sufficient to oppose YAP1. Taken together, our characterisation of LATS2 variants uncovers novel insights into the regulation of LATS kinases in Hippo signalling.
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http://dx.doi.org/10.1016/j.cellsig.2016.02.012DOI Listing
May 2016

STK38 at the crossroad between autophagy and apoptosis.

Autophagy 2016 18;12(3):594-5. Epub 2016 Feb 18.

e INSERM U830, Institut Curie , Paris , France.

We describe the STK38 protein kinase as a conserved regulator of autophagy. We discovered STK38 as a novel binding partner of Beclin1, a key regulator of autophagy. By combining molecular, cell biological and genetic approaches, we show that STK38 promotes autophagosome formation in human cells and in Drosophila. Furthermore, we also provide evidence demonstrating that STK38 with the small GTPase RalB, assist the co-ordination between autophagic and apoptotic events upon autophagy induction, hence proposing a role for STK38 in determining cellular fate in response to autophagic conditions.
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http://dx.doi.org/10.1080/15548627.2015.1135283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835969PMC
December 2016

RASSF1A Suppresses the Invasion and Metastatic Potential of Human Non-Small Cell Lung Cancer Cells by Inhibiting YAP Activation through the GEF-H1/RhoB Pathway.

Cancer Res 2016 Mar 12;76(6):1627-40. Epub 2016 Jan 12.

Normandie Universite, UMR1086 INSERM, Caen, France. Pneumologie et Oncologie thoracique, Hôpital Bichat, France.

Inactivation of the tumor suppressor gene RASSF1A by promoter hypermethylation represents a key event underlying the initiation and progression of lung cancer. RASSF1A inactivation is also associated with poor prognosis and may promote metastatic spread. In this study, we investigated how RASSF1A inactivation conferred invasive phenotypes to human bronchial cells. RNAi-mediated silencing of RASSF1A induced epithelial-to-mesenchymal transition (EMT), fomenting a motile and invasive cellular phenotype in vitro and increased metastatic prowess in vivo. Mechanistic investigations revealed that RASSF1A blocked tumor growth by stimulating cofilin/PP2A-mediated dephosphorylation of the guanine nucleotide exchange factor GEF-H1, thereby stimulating its ability to activate the antimetastatic small GTPase RhoB. Furthermore, RASSF1A reduced nuclear accumulation of the Hippo pathway transcriptional cofactor Yes-associated protein (YAP), which was reinforced by RhoB activation. Collectively, our results indicated that RASSF1 acts to restrict EMT and invasion by indirectly controlling YAP nuclear shuttling and activation through a RhoB-regulated cytoskeletal remodeling process, with potential implications to delay the progression of RASSF1-hypermethylated lung tumors.
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http://dx.doi.org/10.1158/0008-5472.CAN-15-1008DOI Listing
March 2016

The kinases NDR1/2 act downstream of the Hippo homolog MST1 to mediate both egress of thymocytes from the thymus and lymphocyte motility.

Sci Signal 2015 Oct 6;8(397):ra100. Epub 2015 Oct 6.

Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland. Faculty of Science, University of Basel, 4003 Basel, Switzerland.

The serine and threonine kinase MST1 is the mammalian homolog of Hippo. MST1 is a critical mediator of the migration, adhesion, and survival of T cells; however, these functions of MST1 are independent of signaling by its typical effectors, the kinase LATS and the transcriptional coactivator YAP. The kinase NDR1, a member of the same family of kinases as LATS, functions as a tumor suppressor by preventing T cell lymphomagenesis, which suggests that it may play a role in T cell homeostasis. We generated and characterized mice with a T cell-specific double knockout of Ndr1 and Ndr2 (Ndr DKO). Compared with control mice, Ndr DKO mice exhibited a substantial reduction in the number of naïve T cells in their secondary lymphoid organs. Mature single-positive thymocytes accumulated in the thymus in Ndr DKO mice. We also found that NDRs acted downstream of MST1 to mediate the egress of mature thymocytes from the thymus, as well as the interstitial migration of naïve T cells within popliteal lymph nodes. Together, our findings indicate that the kinases NDR1 and NDR2 function as downstream effectors of MST1 to mediate thymocyte egress and T cell migration.
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http://dx.doi.org/10.1126/scisignal.aab2425DOI Listing
October 2015

The Pro-apoptotic STK38 Kinase Is a New Beclin1 Partner Positively Regulating Autophagy.

Curr Biol 2015 Oct 17;25(19):2479-92. Epub 2015 Sep 17.

INSERM U830, Institut Curie, Paris 75248, France. Electronic address:

Autophagy plays key roles in development, oncogenesis, cardiovascular, metabolic, and neurodegenerative diseases. Hence, understanding how autophagy is regulated can reveal opportunities to modify autophagy in a disease-relevant manner. Ideally, one would want to functionally define autophagy regulators whose enzymatic activity can potentially be modulated. Here, we describe the STK38 protein kinase (also termed NDR1) as a conserved regulator of autophagy. Using STK38 as bait in yeast-two-hybrid screens, we discovered STK38 as a novel binding partner of Beclin1, a key regulator of autophagy. By combining molecular, cell biological, and genetic approaches, we show that STK38 promotes autophagosome formation in human cells and in Drosophila. Upon autophagy induction, STK38-depleted cells display impaired LC3B-II conversion; reduced ATG14L, ATG12, and WIPI-1 puncta formation; and significantly decreased Vps34 activity, as judged by PI3P formation. Furthermore, we observed that STK38 supports the interaction of the exocyst component Exo84 with Beclin1 and RalB, which is required to initiate autophagosome formation. Upon studying the activation of STK38 during autophagy induction, we found that STK38 is stimulated in a MOB1- and exocyst-dependent manner. In contrast, RalB depletion triggers hyperactivation of STK38, resulting in STK38-dependent apoptosis under prolonged autophagy conditions. Together, our data establish STK38 as a conserved regulator of autophagy in human cells and flies. We also provide evidence demonstrating that STK38 and RalB assist the coordination between autophagic and apoptotic events upon autophagy induction, hence further proposing a role for STK38 in determining cellular fate in response to autophagic conditions.
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http://dx.doi.org/10.1016/j.cub.2015.08.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598746PMC
October 2015

NDR Kinases Are Essential for Somitogenesis and Cardiac Looping during Mouse Embryonic Development.

PLoS One 2015 25;10(8):e0136566. Epub 2015 Aug 25.

UCL Cancer Institute, University College London, London, United Kingdom.

Studies of mammalian tissue culture cells indicate that the conserved and distinct NDR isoforms, NDR1 and NDR2, play essential cell biological roles. However, mice lacking either Ndr1 or Ndr2 alone develop normally. Here, we studied the physiological consequences of inactivating both NDR1 and NDR2 in mice, showing that the lack of both Ndr1/Ndr2 (called Ndr1/2-double null mutants) causes embryonic lethality. In support of compensatory roles for NDR1 and NDR2, total protein and activating phosphorylation levels of the remaining NDR isoform were elevated in mice lacking either Ndr1 or Ndr2. Mice retaining one single wild-type Ndr allele were viable and fertile. Ndr1/2-double null embryos displayed multiple phenotypes causing a developmental delay from embryonic day E8.5 onwards. While NDR kinases are not required for notochord formation, the somites of Ndr1/2-double null embryos were smaller, irregularly shaped and unevenly spaced along the anterior-posterior axis. Genes implicated in somitogenesis were down-regulated and the normally symmetric expression of Lunatic fringe, a component of the Notch pathway, showed a left-right bias in the last forming somite in 50% of all Ndr1/2-double null embryos. In addition, Ndr1/2-double null embryos developed a heart defect that manifests itself as pericardial edemas, obstructed heart tubes and arrest of cardiac looping. The resulting cardiac insufficiency is the likely cause of the lethality of Ndr1/2-double null embryos around E10. Taken together, we show that NDR kinases compensate for each other in vivo in mouse embryos, explaining why mice deficient for either Ndr1 or Ndr2 are viable. Ndr1/2-double null embryos show defects in somitogenesis and cardiac looping, which reveals their essential functions and shows that the NDR kinases are critically required during the early phase of organogenesis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0136566PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549247PMC
May 2016

Regulation of NDR1 activity by PLK1 ensures proper spindle orientation in mitosis.

Sci Rep 2015 Jun 9;5:10449. Epub 2015 Jun 9.

1] Anhui Key Laboratory of Cellular Dynamics &Chemical Biology and the University of Science and Technology of China, Hefei 230026, China [2] Molecular Imaging Center, Morehouse School of Medicine, Atlanta, GA 30310, USA.

Accurate chromosome segregation during mitosis requires the physical separation of sister chromatids which depends on correct position of mitotic spindle relative to membrane cortex. Although recent work has identified the role of PLK1 in spindle orientation, the mechanisms underlying PLK1 signaling in spindle positioning and orientation have not been fully illustrated. Here, we identified a conserved signaling axis in which NDR1 kinase activity is regulated by PLK1 in mitosis. PLK1 phosphorylates NDR1 at three putative threonine residues (T7, T183 and T407) at mitotic entry, which elicits PLK1-dependent suppression of NDR1 activity and ensures correct spindle orientation in mitosis. Importantly, persistent expression of non-phosphorylatable NDR1 mutant perturbs spindle orientation. Mechanistically, PLK1-mediated phosphorylation protects the binding of Mob1 to NDR1 and subsequent NDR1 activation. These findings define a conserved signaling axis that integrates dynamic kinetochore-microtubule interaction and spindle orientation control to genomic stability maintenance.
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http://dx.doi.org/10.1038/srep10449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4460818PMC
June 2015

NDR functions as a physiological YAP1 kinase in the intestinal epithelium.

Curr Biol 2015 Feb 15;25(3):296-305. Epub 2015 Jan 15.

Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland. Electronic address:

Background: Phosphorylation of the transcriptional coactivator YAP1 is a key event in defining Hippo signaling outputs. Previous studies demonstrated that phosphorylation of YAP1 at serine 127 (S127) sequesters YAP1 in the cytoplasm and consequently inhibits YAP1 transcriptional activity. Mammalian tissue-culture experiments suggest that downstream of MST1/2 signaling, LATS1/2 function as YAP1-S127 kinases. However, studies of Mst1/2 knockout mouse models revealed that the identity of the physiological YAP1-S127 kinase(s) in certain tissues, such as the intestine, remains unknown.

Results: We show that mammalian NDR1/2 kinases phosphorylate YAP1 on S127 and thereby negatively regulate YAP1 activity in tissue-cultured cells. By studying NDR1/2-deficient mice, we demonstrate the in vivo relevance of NDR1/2-mediated regulation of YAP1. Specifically, upon loss of NDR1/2 in the intestinal epithelium, endogenous S127 phosphorylation is decreased whereas total YAP1 levels are increased. Significantly, ablation of NDR1/2 from the intestinal epithelium renders mice exquisitely sensitive to chemically induced colon carcinogenesis. Analysis of human colon cancer samples further revealed that NDR2 and YAP1 protein expression are inversely correlated in the majority of samples with high YAP1 expression. Collectively, we report NDR1/2 as physiological YAP1-S127 kinases that might function as tumor suppressors upstream of YAP1 in human colorectal cancer.

Conclusions: We establish mammalian NDR1/2 as bona fide kinases that target YAP1 on S127 in vitro and in vivo. Our findings therefore have important implications for a broad range of research efforts aimed at decoding and eventually manipulating YAP1 biology in cancer settings, regenerative medicine, and possibly also noncancer human diseases.
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http://dx.doi.org/10.1016/j.cub.2014.11.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426889PMC
February 2015

Regulation of DNA damage responses and cell cycle progression by hMOB2.

Cell Signal 2015 Feb 21;27(2):326-39. Epub 2014 Nov 21.

UCL Cancer Institute, University College London, WC1E 6BT, London, United Kingdom. Electronic address:

Mps one binder proteins (MOBs) are conserved regulators of essential signalling pathways. Biochemically, human MOB2 (hMOB2) can inhibit NDR kinases by competing with hMOB1 for binding to NDRs. However, biological roles of hMOB2 have remained enigmatic. Here, we describe novel functions of hMOB2 in the DNA damage response (DDR) and cell cycle regulation. hMOB2 promotes DDR signalling, cell survival and cell cycle arrest after exogenously induced DNA damage. Under normal growth conditions in the absence of exogenously induced DNA damage hMOB2 plays a role in preventing the accumulation of endogenous DNA damage and a subsequent p53/p21-dependent G1/S cell cycle arrest. Unexpectedly, these molecular and cellular phenotypes are not observed upon NDR manipulations, indicating that hMOB2 performs these functions independent of NDR signalling. Thus, to gain mechanistic insight, we screened for novel binding partners of hMOB2, revealing that hMOB2 interacts with RAD50, facilitating the recruitment of the MRE11-RAD50-NBS1 (MRN) DNA damage sensor complex and activated ATM to DNA damaged chromatin. Taken together, we conclude that hMOB2 supports the DDR and cell cycle progression.
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http://dx.doi.org/10.1016/j.cellsig.2014.11.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276419PMC
February 2015

The Hippo pathway in disease and therapy: cancer and beyond.

Clin Transl Med 2014 10;3:22. Epub 2014 Jul 10.

Tumour Suppressor Signalling Networks laboratory, UCL Cancer Institute, University College London, 72 Huntley Street, WC1E 6BT London, UK.

The Hippo tumour suppressor pathway co-ordinates cell proliferation, cell death and cell differentiation to regulate tissue growth control. In mammals, a conserved core Hippo signalling module receives signal inputs on different levels to ensure the proper regulation of YAP/TAZ activities as transcriptional co-activators. While the core module members MST1/2, Salvador, LATS1/2 and MOB1 have been attributed tumour suppressive functions, YAP/TAZ have been mainly described to have oncogenic roles, although some reports provided evidence supporting growth suppressive roles of YAP/TAZ in certain cancer settings. Intriguingly, mammalian Hippo signalling is also implicated in non-cancer diseases and plays a role in tissue regeneration following injury. Cumulatively, these findings indicate that the pharmacological inhibition or activation of the Hippo pathway could be desirable depending on the disease context. In this review, we first summarise the functions of the mammalian Hippo pathway in tumour formation, and then discuss non-cancer diseases involving Hippo signalling core components with a specific focus on our current understanding of the non-cancer roles of MST1/2 and YAP/TAZ. In addition, the pros and cons of possible pharmacological interventions with Hippo signalling will be reviewed, with particular emphasis on anti-cancer drug development and regenerative medicine.
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http://dx.doi.org/10.1186/2001-1326-3-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107774PMC
August 2014