18,269 results match your criteria The EMBO journal[Journal]


Pten controls B-cell responsiveness and germinal center reaction by regulating the expression of IgD BCR.

EMBO J 2019 Apr 23. Epub 2019 Apr 23.

Institute of Immunology, Ulm University Medical Center, Ulm, Germany

In contrast to other B-cell antigen receptor (BCR) classes, the function of IgD BCR on mature B cells remains largely elusive as mature B cells co-express IgM, which is sufficient for development, survival, and activation of B cells. Here, we show that IgD expression is regulated by the forkhead box transcription factor FoxO1, thereby shifting the responsiveness of mature B cells towards recognition of multivalent antigen. FoxO1 is repressed by phosphoinositide 3-kinase (PI3K) signaling and requires the lipid phosphatase Pten for its activation. Read More

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http://dx.doi.org/10.15252/embj.2018100249DOI Listing

Slx5/Slx8-dependent ubiquitin hotspots on chromatin contribute to stress tolerance.

EMBO J 2019 Apr 23. Epub 2019 Apr 23.

Max Planck Institute of Biochemistry, Molecular Cell Biology, Martinsried, Germany.

Chromatin is a highly regulated environment, and protein association with chromatin is often controlled by post-translational modifications and the corresponding enzymatic machinery. Specifically, SUMO-targeted ubiquitin ligases (STUbLs) have emerged as key players in nuclear quality control, genome maintenance, and transcription. However, how STUbLs select specific substrates among myriads of SUMOylated proteins on chromatin remains unclear. Read More

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http://dx.doi.org/10.15252/embj.2018100368DOI Listing

Local actin nucleation tunes centrosomal microtubule nucleation during passage through mitosis.

EMBO J 2019 Apr 23. Epub 2019 Apr 23.

MRC-LMCB, UCL, London, UK

Cells going through mitosis undergo precisely timed changes in cell shape and organisation, which serve to ensure the fair partitioning of cellular components into the two daughter cells. These structural changes are driven by changes in actin filament and microtubule dynamics and organisation. While most evidence suggests that the two cytoskeletal systems are remodelled in parallel during mitosis, recent work in interphase cells has implicated the centrosome in both microtubule and actin nucleation, suggesting the potential for regulatory crosstalk between the two systems. Read More

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http://dx.doi.org/10.15252/embj.201899843DOI Listing

Cancer cells induce immune escape via glycocalyx changes controlled by the telomeric protein TRF2.

EMBO J 2019 Apr 18. Epub 2019 Apr 18.

Université Côte d'Azur, Centre National de la Recherche Scientifique (CNRS) UMR7284, Institut National de la Santé et de la Recherche Médicale (INSERM) U1081, Institute for Research on Cancer and Aging, Nice (IRCAN), Nice, France

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with strong immunosuppressive activity that promote tumor growth. In this study, we describe a mechanism by which cancer cells control MDSCs in human cancers by upregulating TRF2, a protein required for telomere stability. Specifically, we showed that the TRF2 upregulation in cancer cells has extratelomeric roles in activating the expression of a network of genes involved in the biosynthesis of heparan sulfate proteoglycan, leading to profound changes in glycocalyx length and stiffness, as revealed by atomic force microscopy. Read More

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http://dx.doi.org/10.15252/embj.2018100012DOI Listing

A slow transcription rate causes embryonic lethality and perturbs kinetic coupling of neuronal genes.

EMBO J 2019 Apr 15. Epub 2019 Apr 15.

MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK

The rate of RNA polymerase II (RNAPII) elongation has an important role in the control of alternative splicing (AS); however, the consequences of an altered elongation rate are unknown. Here, we generated mouse embryonic stem cells (ESCs) knocked in for a slow elongating form of RNAPII We show that a reduced transcriptional elongation rate results in early embryonic lethality in mice. Focusing on neuronal differentiation as a model, we observed that slow elongation impairs development of the neural lineage from ESCs, which is accompanied by changes in AS and in gene expression along this pathway. Read More

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http://dx.doi.org/10.15252/embj.2018101244DOI Listing

Chopping GSDMD: caspase-8 has joined the team of pyroptosis-mediating caspases.

EMBO J 2019 Apr 15. Epub 2019 Apr 15.

Immunology Catalyst Programme, GSK, Cambridge, UK.

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http://dx.doi.org/10.15252/embj.2019102065DOI Listing

Regulation of death receptor signaling by the autophagy protein TP53INP2.

EMBO J 2019 Apr 12. Epub 2019 Apr 12.

Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

TP53INP2 positively regulates autophagy by binding to Atg8 proteins. Here, we uncover a novel role of TP53INP2 in death-receptor signaling. TP53INP2 sensitizes cells to apoptosis induced by death receptor ligands. Read More

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http://emboj.embopress.org/lookup/doi/10.15252/embj.20189930
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http://dx.doi.org/10.15252/embj.201899300DOI Listing
April 2019
2 Reads

A non-death function of the mitochondrial apoptosis apparatus in immunity.

EMBO J 2019 Apr 12. Epub 2019 Apr 12.

Faculty of Medicine, Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Freiburg, Germany

Apoptosis is a frequent form of programmed cell death, but the apoptotic signaling pathway can also be engaged at a low level, in the absence of cell death. We here report that such sub-lethal engagement of mitochondrial apoptosis signaling causes the secretion of cytokines from human epithelial cells in a process controlled by the Bcl-2 family of proteins. We further show that sub-lethal signaling of the mitochondrial apoptosis pathway is initiated by infections with all tested viral, bacterial, and protozoan pathogens and causes damage to the genomic DNA. Read More

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http://dx.doi.org/10.15252/embj.2018100907DOI Listing
April 2019
4 Reads

Co-degradation of interferon signaling factor DDX3 by PB1-F2 as a basis for high virulence of 1918 pandemic influenza.

EMBO J 2019 Apr 12. Epub 2019 Apr 12.

Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea

The multifunctional influenza virus protein PB1-F2 plays several roles in deregulation of host innate immune responses and is a known immunopathology enhancer of the 1918 influenza pandemic. Here, we show that the 1918 PB1-F2 protein not only interferes with the mitochondria-dependent pathway of type I interferon (IFN) signaling, but also acquired a novel IFN antagonist function by targeting the DEAD-box helicase DDX3, a key downstream mediator in antiviral interferon signaling, toward proteasome-dependent degradation. Interactome analysis revealed that 1918 PB1-F2, but not PR8 PB1-F2, binds to DDX3 and causes its co-degradation. Read More

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http://emboj.embopress.org/lookup/doi/10.15252/embj.20189947
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http://dx.doi.org/10.15252/embj.201899475DOI Listing
April 2019
1 Read

YY1 regulates skeletal muscle regeneration through controlling metabolic reprogramming of satellite cells.

EMBO J 2019 Apr 12. Epub 2019 Apr 12.

Department of Orthopedics and Traumatology, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China

Skeletal muscle satellite cells (SCs) are adult muscle stem cells responsible for muscle regeneration after acute or chronic injuries. The lineage progression of quiescent SC toward activation, proliferation, and differentiation during the regeneration is orchestrated by cascades of transcription factors (TFs). Here, we elucidate the function of TF Yin Yang1 (YY1) in muscle regeneration. Read More

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http://dx.doi.org/10.15252/embj.201899727DOI Listing
April 2019
2 Reads
10.434 Impact Factor

The yeast mitochondrial pyruvate carrier is a hetero-dimer in its functional state.

EMBO J 2019 Apr 12. Epub 2019 Apr 12.

Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK

The mitochondrial pyruvate carrier (MPC) is critical for cellular homeostasis, as it is required in central metabolism for transporting pyruvate from the cytosol into the mitochondrial matrix. MPC has been implicated in many diseases and is being investigated as a drug target. A few years ago, small membrane proteins, called MPC1 and MPC2 in mammals and Mpc1, Mpc2 and Mpc3 in yeast, were proposed to form large protein complexes responsible for this function. Read More

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http://dx.doi.org/10.15252/embj.2018100785DOI Listing

A choreography of intracellular Ca and extracellular ATP to refine auditory nociceptors before hearing.

EMBO J 2019 Apr 11. Epub 2019 Apr 11.

Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps-University Marburg, Marburg, Germany.

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http://dx.doi.org/10.15252/embj.2019101980DOI Listing

A supporting ecosystem to mature extracellular vesicles into clinical application.

EMBO J 2019 Apr 11. Epub 2019 Apr 11.

Laboratory of Experimental Cancer Research, Department of Human Structure and Repair Ghent University, Ghent, Belgium.

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http://dx.doi.org/10.15252/embj.2018101412DOI Listing

Lining up for quality control: linear ubiquitin and proteotoxicity.

Authors:
R Luke Wiseman

EMBO J 2019 Apr 11. Epub 2019 Apr 11.

Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.

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http://dx.doi.org/10.15252/embj.2019101985DOI Listing

OTUB1 inhibits CNS autoimmunity by preventing IFN-γ-induced hyperactivation of astrocytes.

EMBO J 2019 Apr 3. Epub 2019 Apr 3.

Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke University Magdeburg, Magdeburg, Germany

Astrocytes are critical regulators of neuroinflammation in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Growing evidence indicates that ubiquitination of signaling molecules is an important cell-intrinsic mechanism governing astrocyte function during MS and EAE Here, we identified an upregulation of the deubiquitinase OTU domain, ubiquitin aldehyde binding 1 (OTUB1) in astrocytes during MS and EAE Mice with astrocyte-specific OTUB1 ablation developed more severe EAE due to increased leukocyte accumulation, proinflammatory gene transcription, and demyelination in the spinal cord as compared to control mice. OTUB1-deficient astrocytes were hyperactivated in response to IFN-γ, a fingerprint cytokine of encephalitogenic T cells, and produced more proinflammatory cytokines and chemokines than control astrocytes. Read More

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http://dx.doi.org/10.15252/embj.2018100947DOI Listing
April 2019
2 Reads

Binding of IFT22 to the intraflagellar transport complex is essential for flagellum assembly.

EMBO J 2019 Apr 2. Epub 2019 Apr 2.

Department of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark

Intraflagellar transport (IFT) relies on motor proteins and the IFT complex to construct cilia and flagella. The IFT complex subunit IFT22/RabL5 has sequence similarity with small GTPases although the nucleotide specificity is unclear because of non-conserved G4/G5 motifs. We show that IFT22 specifically associates with G-nucleotides and present crystal structures of IFT22 in complex with GDP, GTP, and with IFT74/81. Read More

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http://dx.doi.org/10.15252/embj.2018101251DOI Listing
April 2019
3 Reads

Intrinsic lipid binding activity of ATG16L1 supports efficient membrane anchoring and autophagy.

EMBO J 2019 Apr 1. Epub 2019 Apr 1.

Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK

Membrane targeting of autophagy-related complexes is an important step that regulates their activities and prevents their aberrant engagement on non-autophagic membranes. ATG16L1 is a core autophagy protein implicated at distinct phases of autophagosome biogenesis. In this study, we dissected the recruitment of ATG16L1 to the pre-autophagosomal structure (PAS) and showed that it requires sequences within its coiled-coil domain (CCD) dispensable for homodimerisation. Read More

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http://dx.doi.org/10.15252/embj.2018100554DOI Listing

To Fis or not to Fuse? This is the question!

EMBO J 2019 Apr 1;38(8). Epub 2019 Apr 1.

Departments of Medicine, Endocrinology and Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

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http://emboj.embopress.org/lookup/doi/10.15252/embj.20191018
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http://dx.doi.org/10.15252/embj.2019101839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463207PMC
April 2019
2 Reads

The long noncoding RNA regulates inflammatory gene expression.

EMBO J 2019 Apr 27;38(8). Epub 2019 Mar 27.

Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA

Long noncoding RNAs (lncRNAs) can regulate target gene expression by acting in (locally) or in (non-locally). Here, we performed genome-wide expression analysis of Toll-like receptor (TLR)-stimulated human macrophages to identify pairs of -acting lncRNAs and protein-coding genes involved in innate immunity. A total of 229 gene pairs were identified, many of which were commonly regulated by signaling through multiple TLRs and were involved in the cytokine responses to infection by group B We focused on elucidating the function of one lncRNA, named or (Regulator of Cytokines and Inflammation), which was induced by multiple TLR stimuli and acted as a master regulator of inflammatory responses. Read More

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http://dx.doi.org/10.15252/embj.2018100041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463213PMC

Pancreatic development: one cell at a (pseudo)time.

EMBO J 2019 Apr 26;38(8). Epub 2019 Mar 26.

Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.

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http://dx.doi.org/10.15252/embj.2019101891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463208PMC

SUMOylation promotes protective responses to DNA-protein crosslinks.

EMBO J 2019 Apr 26;38(8). Epub 2019 Mar 26.

Ubiquitin Signaling Group, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark

DNA-protein crosslinks (DPCs) are highly cytotoxic lesions that obstruct essential DNA transactions and whose resolution is critical for cell and organismal fitness. However, the mechanisms by which cells respond to and overcome DPCs remain incompletely understood. Recent studies unveiled a dedicated DPC repair pathway in higher eukaryotes involving the SprT-type metalloprotease SPRTN/DVC1, which proteolytically processes DPCs during DNA replication in a ubiquitin-regulated manner. Read More

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http://dx.doi.org/10.15252/embj.2019101496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463212PMC

Asymmetric distribution of glucose transporter mRNA provides a growth advantage in yeast.

EMBO J 2019 Mar 25. Epub 2019 Mar 25.

Biozentrum, University of Basel, Basel, Switzerland

Asymmetric localization of mRNA is important for cell fate decisions in eukaryotes and provides the means for localized protein synthesis in a variety of cell types. Here, we show that hexose transporter mRNAs are retained in the mother cell of until metaphase-anaphase transition (MAT) and then are released into the bud. The retained mRNA was translationally less active but bound to ribosomes before MAT Importantly, when cells were shifted from starvation to glucose-rich conditions, HXT2 mRNA, but none of the other HXT mRNAs, was enriched in the bud after MAT This enrichment was dependent on the Ras/cAMP/PKA pathway, the APC ortholog Kar9, and nuclear segregation into the bud. Read More

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http://dx.doi.org/10.15252/embj.2018100373DOI Listing

Extrinsic and intrinsic apoptosis activate pannexin-1 to drive NLRP3 inflammasome assembly.

EMBO J 2019 Mar 22. Epub 2019 Mar 22.

Department of Biochemistry, University of Lausanne, Epalinges, Switzerland

Pyroptosis is a form of lytic inflammatory cell death driven by inflammatory caspase-1, caspase-4, caspase-5 and caspase-11. These caspases cleave and activate the pore-forming protein gasdermin D (GSDMD) to induce membrane damage. By contrast, apoptosis is driven by apoptotic caspase-8 or caspase-9 and has traditionally been classified as an immunologically silent form of cell death. Read More

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http://dx.doi.org/10.15252/embj.2019101638DOI Listing

Actin filaments regulate microtubule growth at the centrosome.

EMBO J 2019 Mar 22. Epub 2019 Mar 22.

CEA, CNRS, INRA, Biosciences & Biotechnology Institute of Grenoble, UMR5168, CytoMorpho Lab, Univ. Grenoble-Alpes, Grenoble, France

The centrosome is the main microtubule-organizing centre. It also organizes a local network of actin filaments. However, the precise function of the actin network at the centrosome is not well understood. Read More

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http://dx.doi.org/10.15252/embj.201899630DOI Listing

TRAF6 directs FOXP3 localization and facilitates regulatory T-cell function through K63-linked ubiquitination.

EMBO J 2019 Mar 18. Epub 2019 Mar 18.

Translational Medicine Research Center of Affiliated Jiangning Hospital, Liver Transplantation Center of First Affiliated Hospital, and Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, Jiangsu, China

Regulatory T cells (Tregs) are crucial mediators of immune control. The characteristic gene expression and suppressive functions of Tregs depend considerably on the stable expression and activity of the transcription factor FOXP3. Transcriptional regulation of the Foxp3 gene has been studied in depth, but both the expression and function of this factor are also modulated at the protein level. Read More

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http://dx.doi.org/10.15252/embj.201899766DOI Listing
March 2019
1 Read
10.434 Impact Factor

Mutant Lef1 controls Gata6 in sebaceous gland development and cancer.

EMBO J 2019 Mar 18. Epub 2019 Mar 18.

Centre for Stem Cells and Regenerative Medicine, King's College London, London, UK

Mutations in Lef1 occur in human and mouse sebaceous gland (SG) tumors, but their contribution to carcinogenesis remains unclear. Since Gata6 controls lineage identity in SG, we investigated the link between these two transcription factors. Here, we show that Gata6 is a β-catenin-independent transcriptional target of mutant Lef1. Read More

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http://dx.doi.org/10.15252/embj.2018100526DOI Listing

A protein quality control pathway regulated by linear ubiquitination.

EMBO J 2019 Mar 18. Epub 2019 Mar 18.

Department of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum, Germany

Neurodegenerative diseases are characterized by the accumulation of misfolded proteins in the brain. Insights into protein quality control mechanisms to prevent neuronal dysfunction and cell death are crucial in developing causal therapies. Here, we report that various disease-associated protein aggregates are modified by the linear ubiquitin chain assembly complex (LUBAC). Read More

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http://dx.doi.org/10.15252/embj.2018100730DOI Listing

Protein translocation by the SecA ATPase occurs by a power-stroke mechanism.

EMBO J 2019 Mar 15. Epub 2019 Mar 15.

Department of Cell Biology, Harvard Medical School, Boston, MA, USA

SecA belongs to the large class of ATPases that use the energy of ATP hydrolysis to perform mechanical work resulting in protein translocation across membranes, protein degradation, and unfolding. SecA translocates polypeptides through the SecY membrane channel during protein secretion in bacteria, but how it achieves directed peptide movement is unclear. Here, we use single-molecule FRET to derive a model that couples ATP hydrolysis-dependent conformational changes of SecA with protein translocation. Read More

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http://emboj.embopress.org/lookup/doi/10.15252/embj.20181011
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http://dx.doi.org/10.15252/embj.2018101140DOI Listing
March 2019
9 Reads

and high-resolution cryo-EM structure of a bacterial type VI secretion system membrane complex.

EMBO J 2019 Mar 15. Epub 2019 Mar 15.

CNRS UMR 5234 Microbiologie Fondamentale et Pathogénicité, Bordeaux, France

Bacteria have evolved macromolecular machineries that secrete effectors and toxins to survive and thrive in diverse environments. The type VI secretion system (T6SS) is a contractile machine that is related to phages. It is composed of a phage tail-like structure inserted in the bacterial cell envelope by a membrane complex (MC) comprising the TssJ, TssL and TssM proteins. Read More

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http://dx.doi.org/10.15252/embj.2018100886DOI Listing

Slicing and dicing viruses: antiviral RNA interference in mammals.

EMBO J 2019 Apr 14;38(8). Epub 2019 Mar 14.

Immunobiology Laboratory, The Francis Crick Institute, London, UK

To protect against the harmful consequences of viral infections, organisms are equipped with sophisticated antiviral mechanisms, including cell-intrinsic means to restrict viral replication and propagation. Plant and invertebrate cells utilise mostly RNA interference (RNAi), an RNA-based mechanism, for cell-intrinsic immunity to viruses while vertebrates rely on the protein-based interferon (IFN)-driven innate immune system for the same purpose. The RNAi machinery is conserved in vertebrate cells, yet whether antiviral RNAi is still active in mammals and functionally relevant to mammalian antiviral defence is intensely debated. Read More

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http://emboj.embopress.org/lookup/doi/10.15252/embj.20181009
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http://dx.doi.org/10.15252/embj.2018100941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463209PMC
April 2019
8 Reads

Phosphatidylinositol 4,5-bisphosphate controls Rab7 and PLEKMH1 membrane cycling during autophagosome-lysosome fusion.

EMBO J 2019 Apr 13;38(8). Epub 2019 Mar 13.

Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

The small GTPase Rab7 is a key organizer of receptor sorting and lysosomal degradation by recruiting of a variety of effectors depending on its GDP/GTP-bound state. However, molecular mechanisms that trigger Rab7 inactivation remain elusive. Here we find that, among the endosomal pools, Rab7-positive compartments possess the highest level of PI4P, which is primarily produced by PI4K2A kinase. Read More

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http://dx.doi.org/10.15252/embj.2018100312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463214PMC

Cideb controls sterol-regulated ER export of SREBP/SCAP by promoting cargo loading at ER exit sites.

EMBO J 2019 Apr 11;38(8). Epub 2019 Mar 11.

State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China

SREBPs are master regulators of lipid homeostasis and undergo sterol-regulated export from ER to Golgi apparatus for processing and activation via COPII-coated vesicles. While COPII recognizes SREBP through its escort protein SCAP, factor(s) specifically promoting SREBP/SCAP loading to the COPII machinery remains unknown. Here, we show that the ER/lipid droplet-associated protein Cideb selectively promotes the loading of SREBP/SCAP into COPII vesicles. Read More

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http://dx.doi.org/10.15252/embj.2018100156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463267PMC
April 2019
1 Read

ALYREF links 3'-end processing to nuclear export of non-polyadenylated mRNAs.

EMBO J 2019 Mar 11. Epub 2019 Mar 11.

State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences University of Chinese Academy of Sciences, Shanghai, China

The RNA-binding protein ALYREF plays key roles in nuclear export and also 3'-end processing of polyadenylated mRNAs, but whether such regulation also extends to non-polyadenylated RNAs is unknown. Replication-dependent (RD)-histone mRNAs are not polyadenylated, but instead end in a stem-loop (SL) structure. Here, we demonstrate that ALYREF prevalently binds a region next to the SL on RD-histone mRNAs. Read More

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http://dx.doi.org/10.15252/embj.201899910DOI Listing
March 2019
3 Reads
10.434 Impact Factor

Extracellular matrix sensing by FERONIA and Leucine-Rich Repeat Extensins controls vacuolar expansion during cellular elongation in .

EMBO J 2019 Apr 8;38(7). Epub 2019 Mar 8.

Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences (BOKU), Vienna, Austria

Cellular elongation requires the defined coordination of intra- and extracellular processes, but the underlying mechanisms are largely unknown. The vacuole is the biggest plant organelle, and its dimensions play a role in defining plant cell expansion rates. Here, we show that the increase in vacuolar occupancy enables cellular elongation with relatively little enlargement of the cytosol in We demonstrate that cell wall properties are sensed and impact on the intracellular expansion of the vacuole. Read More

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http://dx.doi.org/10.15252/embj.2018100353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443208PMC

Bub1-the zombie protein that CRISPR cannot kill.

Authors:
Patrick Meraldi

EMBO J 2019 Apr 8;38(7). Epub 2019 Mar 8.

Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

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http://dx.doi.org/10.15252/embj.2019101912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443206PMC

A spatiotemporally regulated transcriptional complex underlies heteroblastic development of leaf hairs in .

EMBO J 2019 Apr 6;38(8). Epub 2019 Mar 6.

National Key Laboratory of Plant Molecular Genetics (NKLPMG), CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology (SIPPE), Chinese Academy of Sciences (CAS), Shanghai, China

Heteroblasty refers to a phenomenon that a plant produces morphologically or functionally different lateral organs in an age-dependent manner. In the model plant , the production of trichomes (epidermal leaf hairs) on the abaxial (lower) side of leaves is a heteroblastic mark for the juvenile-to-adult transition. Here, we show that the heteroblastic development of abaxial trichomes is regulated by a spatiotemporally regulated complex comprising the leaf abaxial fate determinant () and the developmental timer (miR172-targeted AP2-like proteins). Read More

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http://dx.doi.org/10.15252/embj.2018100063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463210PMC
April 2019
17 Reads
10.434 Impact Factor

BRD4 directs hematopoietic stem cell development and modulates macrophage inflammatory responses.

EMBO J 2019 Apr 6;38(7). Epub 2019 Mar 6.

Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, MD, USA

BRD4 is a BET family protein that binds acetylated histones and regulates transcription. BET/BRD4 inhibitors block blood cancer growth and inflammation and serve as a new therapeutic strategy. However, the biological role of BRD4 in normal hematopoiesis and inflammation is not fully understood. Read More

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http://dx.doi.org/10.15252/embj.2018100293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443207PMC
April 2019
7 Reads

Human Fis1 regulates mitochondrial dynamics through inhibition of the fusion machinery.

EMBO J 2019 Apr 6;38(8). Epub 2019 Mar 6.

Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden

Mitochondrial dynamics is important for life. At center stage for mitochondrial dynamics, the balance between mitochondrial fission and fusion is a set of dynamin-related GTPases that drive mitochondrial fission and fusion. Fission is executed by the GTPases Drp1 and Dyn2, whereas the GTPases Mfn1, Mfn2, and OPA1 promote fusion. Read More

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http://dx.doi.org/10.15252/embj.201899748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463211PMC

Hfq-dependent mRNA unfolding promotes sRNA-based inhibition of translation.

EMBO J 2019 Apr 4;38(7). Epub 2019 Mar 4.

Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Uppsala, Sweden

Small RNAs post-transcriptionally regulate many processes in bacteria. Base-pairing of sRNAs near ribosome-binding sites in mRNAs inhibits translation, often requiring the RNA chaperone Hfq. In the canonical model, Hfq simultaneously binds sRNAs and mRNA targets to accelerate pairing. Read More

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http://dx.doi.org/10.15252/embj.2018101199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443205PMC
April 2019
5 Reads

Revealing chromatin organization in metaphase chromosomes.

Authors:
Beat Fierz

EMBO J 2019 Apr 4;38(7). Epub 2019 Mar 4.

École Polytechnique Fédérale de Lausanne, SB ISIC LCBM, Lausanne, Switzerland.

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http://dx.doi.org/10.15252/embj.2019101699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443199PMC

The pluripotency factor NANOG controls primitive hematopoiesis and directly regulates .

EMBO J 2019 Apr 27;38(7). Epub 2019 Feb 27.

Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain

Progenitors of the first hematopoietic cells in the mouse arise in the early embryo from -positive multipotent cells in the posterior-proximal region of the epiblast, but the mechanisms that specify primitive blood cells are still largely unknown. Pluripotency factors maintain uncommitted cells of the blastocyst and embryonic stem cells in the pluripotent state. However, little is known about the role played by these factors during later development, despite being expressed in the postimplantation epiblast. Read More

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http://emboj.embopress.org/lookup/doi/10.15252/embj.20189912
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http://dx.doi.org/10.15252/embj.201899122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443201PMC
April 2019
7 Reads

An ancient antisense-driven RNA switch drives plant sex determination.

EMBO J 2019 Mar 26;38(6). Epub 2019 Feb 26.

Gregor Mendel Institute (GMI), Vienna Biocenter (VBC), Austrian Academy of Sciences, Vienna, Austria.

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http://dx.doi.org/10.15252/embj.2019101685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418420PMC

Histidine is selectively required for the growth of Myc-dependent dedifferentiation tumours in the CNS.

EMBO J 2019 Apr 25;38(7). Epub 2019 Feb 25.

Peter MacCallum Cancer Centre, Parkville, Vic., Australia

Rewired metabolism of glutamine in cancer has been well documented, but less is known about other amino acids such as histidine. Here, we use cancer models to show that decreasing the concentration of histidine in the diet strongly inhibits the growth of mutant clones induced by loss of Nerfin-1 or gain of Notch activity. In contrast, changes in dietary histidine have much less effect on the growth of wildtype neural stem cells and neural tumours. Read More

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http://emboj.embopress.org/lookup/doi/10.15252/embj.20189989
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http://dx.doi.org/10.15252/embj.201899895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443203PMC
April 2019
5 Reads

Coordinated calcium signalling in cochlear sensory and non-sensory cells refines afferent innervation of outer hair cells.

EMBO J 2019 Feb 25. Epub 2019 Feb 25.

Department of Biomedical Science, University of Sheffield, Sheffield, UK

Outer hair cells (OHCs) are highly specialized sensory cells conferring the fine-tuning and high sensitivity of the mammalian cochlea to acoustic stimuli. Here, by genetically manipulating spontaneous Ca signalling in mice through a period of early postnatal development, we find that the refinement of OHC afferent innervation is regulated by complementary spontaneous Ca signals originating in OHCs and non-sensory cells. OHCs fire spontaneous Ca action potentials during a narrow period of neonatal development. Read More

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http://dx.doi.org/10.15252/embj.201899839DOI Listing
February 2019
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Unanchored tri-NEDD8 inhibits PARP-1 to protect from oxidative stress-induced cell death.

EMBO J 2019 Mar 25;38(6). Epub 2019 Feb 25.

Henry Wellcome Lab of Cell Biology, College of Medical, Veterinary and Life Sciences, Institute of Molecular, Cell and Systems Biology, University of Glasgow, Glasgow, UK

NEDD8 is a ubiquitin-like protein that activates cullin-RING E3 ubiquitin ligases (CRLs). Here, we identify a novel role for NEDD8 in regulating the activity of poly(ADP-ribose) polymerase 1 (PARP-1) in response to oxidative stress. We show that treatment of cells with HO results in the accumulation of NEDD8 chains, likely by directly inhibiting the deneddylase NEDP1. Read More

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http://dx.doi.org/10.15252/embj.2018100024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418418PMC
March 2019
4 Reads

Ssu72 phosphatase is a conserved telomere replication terminator.

EMBO J 2019 Apr 21;38(7). Epub 2019 Feb 21.

Instituto Gulbenkian de Ciência, Oeiras, Portugal

Telomeres, the protective ends of eukaryotic chromosomes, are replicated through concerted actions of conventional DNA polymerases and elongated by telomerase, but the regulation of this process is not fully understood. Telomere replication requires (Ctc1/Cdc13)-Stn1-Ten1, a telomeric ssDNA-binding complex homologous to RPA Here, we show that the evolutionarily conserved phosphatase Ssu72 is responsible for terminating the cycle of telomere replication in fission yeast. Ssu72 controls the recruitment of Stn1 to telomeres by regulating Stn1 phosphorylation at Ser74, a residue located within its conserved OB-fold domain. Read More

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http://dx.doi.org/10.15252/embj.2018100476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443209PMC
April 2019
2 Reads

Multi-omics identify xanthine as a pro-survival metabolite for nematodes with mitochondrial dysfunction.

EMBO J 2019 Mar 22;38(6). Epub 2019 Feb 22.

German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

Aberrant mitochondrial function contributes to the pathogenesis of various metabolic and chronic disorders. Inhibition of insulin/IGF-1 signaling (IIS) represents a promising avenue for the treatment of mitochondrial diseases, although many of the molecular mechanisms underlying this beneficial effect remain elusive. Using an unbiased multi-omics approach, we report here that IIS inhibition reduces protein synthesis and favors catabolism in mitochondrial deficient We unveil that the lifespan extension does not occur through the restoration of mitochondrial respiration, but as a consequence of an ATP-saving metabolic rewiring that is associated with an evolutionarily conserved phosphoproteome landscape. Read More

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http://dx.doi.org/10.15252/embj.201899558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418696PMC
March 2019
1 Read

ABRO1 promotes NLRP3 inflammasome activation through regulation of NLRP3 deubiquitination.

EMBO J 2019 Mar 20;38(6). Epub 2019 Feb 20.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China

Deubiquitination of NLRP3 has been suggested to contribute to inflammasome activation, but the roles and molecular mechanisms are still unclear. We here demonstrate that ABRO1, a subunit of the BRISC deubiquitinase complex, is necessary for optimal NLRP3-ASC complex formation, ASC oligomerization, caspase-1 activation, and IL-1β and IL-18 production upon treatment with NLRP3 ligands after the priming step, indicating that efficient NLRP3 activation requires ABRO1. Moreover, we report that ABRO1 deficiency results in a remarkable attenuation in the syndrome severity of NLRP3-associated inflammatory diseases, including MSU- and Alum-induced peritonitis and LPS-induced sepsis in mice. Read More

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http://dx.doi.org/10.15252/embj.2018100376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418445PMC
March 2019
8 Reads

Boosting adult neurogenesis to enhance sensory performance.

EMBO J 2019 Mar 20;38(6). Epub 2019 Feb 20.

Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK.

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http://dx.doi.org/10.15252/embj.2019101589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418449PMC