Pubfacts - Scientific Publication Data
  • Categories
  • |
  • Journals
  • |
  • Authors
  • Login
  • Categories
  • Journals

Search Our Scientific Publications & Authors

Publications
  • Publications
  • Authors
find publications by category +
Translate page:

The RanBP2/RanGAP1-SUMO complex gates β-arrestin2 nuclear entry to regulate the Mdm2-p53 signaling axis.

Authors:
Elodie Blondel-Tepaz Marie Leverve Badr Sokrat Justine S Paradis Milena Kosic Kusumika Saha Cédric Auffray Evelyne Lima-Fernandes Alessia Zamborlini Anne Poupon Louis Gaboury Jane Findlay George S Baillie Hervé Enslen Michel Bouvier Stéphane Angers Stefano Marullo Mark G H Scott

Oncogene 2021 Mar 1;40(12):2243-2257. Epub 2021 Mar 1.

Inserm, U1016, Institut Cochin, Paris, France.

Mdm2 antagonizes the tumor suppressor p53. Targeting the Mdm2-p53 interaction represents an attractive approach for the treatment of cancers with functional p53. Investigating mechanisms underlying Mdm2-p53 regulation is therefore important. The scaffold protein β-arrestin2 (β-arr2) regulates tumor suppressor p53 by counteracting Mdm2. β-arr2 nucleocytoplasmic shuttling displaces Mdm2 from the nucleus to the cytoplasm resulting in enhanced p53 signaling. β-arr2 is constitutively exported from the nucleus, via a nuclear export signal, but mechanisms regulating its nuclear entry are not completely elucidated. β-arr2 can be SUMOylated, but no information is available on how SUMO may regulate β-arr2 nucleocytoplasmic shuttling. While we found β-arr2 SUMOylation to be dispensable for nuclear import, we identified a non-covalent interaction between SUMO and β-arr2, via a SUMO interaction motif (SIM), that is required for β-arr2 cytonuclear trafficking. This SIM promotes association of β-arr2 with the multimolecular RanBP2/RanGAP1-SUMO nucleocytoplasmic transport hub that resides on the cytoplasmic filaments of the nuclear pore complex. Depletion of RanBP2/RanGAP1-SUMO levels result in defective β-arr2 nuclear entry. Mutation of the SIM inhibits β-arr2 nuclear import, its ability to delocalize Mdm2 from the nucleus to the cytoplasm and enhanced p53 signaling in lung and breast tumor cell lines. Thus, a β-arr2 SIM nuclear entry checkpoint, coupled with active β-arr2 nuclear export, regulates its cytonuclear trafficking function to control the Mdm2-p53 signaling axis.

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41388-021-01704-wDOI Listing
March 2021

Publication Analysis

Top Keywords

nuclear entry
16
β-arr2
13
β-arr2 nuclear
12
nuclear
9
nucleus cytoplasm
8
suppressor p53
8
mdm2-p53 signaling
8
signaling axis
8
tumor suppressor
8
mdm2 nucleus
8
cytoplasm enhanced
8
p53 signaling
8
enhanced p53
8
nuclear export
8
nuclear import
8
β-arr2 nucleocytoplasmic
8
nucleocytoplasmic shuttling
8
cytonuclear trafficking
8
p53
5
β-arr2 sumo
4

Keyword Occurance

Similar Publications

RNA Kinase CLP1/Cbc Regulates Meiosis Initiation in Spermatogenesis.

Authors:
Wu Jianbo Li Xin Gao Zhiyang Pang Lin Liu Xian Huang Xiahe Wang Yingchun Wang Zhaohui

Hum Mol Genet 2021 Apr 16. Epub 2021 Apr 16.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences.

CLP1, TSEN complex, and VCP are evolutionarily conserved proteins whose mutations are associated with neurodegenerative diseases. In this study, we have found that they are also involved in germline differentiation. To optimize both quantity and quality in gametes production, germ cells expand themselves through limited mitotic cycles prior to meiosis. Read More

View Article and Full-Text PDF
April 2021
Similar Publications

Nuts and bolts of the salt-inducible kinases (SIKs).

Authors:
Nicola J Darling Philip Cohen

Biochem J 2021 Apr;478(7):1377-1397

MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, U.K.

The salt-inducible kinases, SIK1, SIK2 and SIK3, most closely resemble the AMP-activated protein kinase (AMPK) and other AMPK-related kinases, and like these family members they require phosphorylation by LKB1 to be catalytically active. However, unlike other AMPK-related kinases they are phosphorylated by cyclic AMP-dependent protein kinase (PKA), which promotes their binding to 14-3-3 proteins and inactivation. The most well-established substrates of the SIKs are the CREB-regulated transcriptional co-activators (CRTCs), and the Class 2a histone deacetylases (HDAC4/5/7/9). Read More

View Article and Full-Text PDF
April 2021
Similar Publications

A trimeric hydrophobic zipper mediates the intramembrane assembly of SARS-CoV-2 spike.

Authors:
Qingshan Fu James J Chou

bioRxiv 2021 Apr 10. Epub 2021 Apr 10.

The S protein of the SARS-CoV-2 is a Type I membrane protein that mediates membrane fusion and viral entry. A vast amount of structural information is available for the ectodomain of S, a primary target by the host immune system, but much less is known regarding its transmembrane domain (TMD) and its membrane-proximal regions. Here, we determined the nuclear magnetic resonance (NMR) structure of the S protein TMD in bicelles that closely mimic a lipid bilayer. Read More

View Article and Full-Text PDF
April 2021
Similar Publications

Deletion of ER-retention Motif on SARS-CoV-2 Spike Protein Reduces Cell Hybrid During Cell-cell Fusion.

Authors:
Chih-Hsiung Chen Saiaditya Badeti Jong Hyun Cho Alireza Naghizadeh Xuening Wang Dongfang Liu

Res Sq 2021 Apr 9. Epub 2021 Apr 9.

The novel SARS-CoV-2 has quickly become a global pandemic since the first reported case in December 2019, with the virus infecting millions of people to date. The spike (S) protein of the SARS-CoV-2 virus plays a key role in binding to angiotensin-converting enzyme 2 (ACE2), a host cell receptor for SARS-CoV-2. S proteins that are expressed on the cell membrane can initiate receptor-dependent syncytia formation that is associated with extensive tissue damage. Read More

View Article and Full-Text PDF
April 2021
Similar Publications

MicroRNA‑29‑3p regulates the β‑catenin pathway by targeting IGF1 to inhibit the proliferation of prolactinoma cells.

Authors:
Jie Xia Songmei Li Dianfei Ma Wenyujie Guo Hong Long Weiping Yin

Mol Med Rep 2021 Jun 13;23(6). Epub 2021 Apr 13.

Department of Pediatrics, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan 650500, P.R. China.

The present study aimed to analyze the effects and underlying mechanisms of microRNA (miR)‑29‑3p on the proliferation and secretory abilities of prolactinoma cells by targeting insulin‑like growth factor (IGF)‑1/β‑catenin. The relationship between miR‑29a‑3p and the survival of prolactinoma cells was analyzed with the Kaplan‑Meier method in reference to The Cancer Genome Atlas. The expression levels of miR‑29a‑3p and IGF‑1 in MMQ and GH3 cells were detected. Read More

View Article and Full-Text PDF
June 2021
Similar Publications
© 2021 PubFacts.
  • About PubFacts
  • Privacy Policy
  • Sitemap