18,216 results match your criteria The EMBO journal[Journal]


STAT4 activation by leukemia inhibitory factor confers a therapeutic effect on intestinal inflammation.

EMBO J 2019 Feb 15. Epub 2019 Feb 15.

Institutes of Biology and Medical Sciences, Soochow University Medical College, Suzhou, Jiangsu, China

T helper 17 (Th17)-cell differentiation triggered by interleukin-6 (IL-6) via STAT3 activation promotes inflammation in inflammatory bowel disease (IBD) patients. However, leukemia inhibitory factor (LIF), an IL-6 family cytokine, restricts inflammation by blocking Th17-cell differentiation via an unknown mechanism. Here, we report that microbiota dysregulation promotes LIF secretion by intestinal epithelial cells (IECs) in a mouse colitis model. Read More

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http://dx.doi.org/10.15252/embj.201899595DOI Listing
February 2019

Ubiquitin-a beacon for all during quality control on the ribosome.

EMBO J 2019 Feb 15. Epub 2019 Feb 15.

Department of Biology, Washington University in St. Louis, St. Louis, MO, USA.

Ribosome stalling triggers no-go decay (NGD) and ribosome-associated quality control (RQC) pathways to rapidly degrade the aberrant mRNA and the incomplete nascent peptide, respectively. Two recent studies in yeast and mammalian systems reveal the importance of stalling-induced ribosomal protein ubiquitination by Hel2/ZNF598 for both NGD and RQC The studies also structurally explain how collided ribosomes generate a unique interface not present in monosomes, which can be recognized by Hel2/ZNF598 ubiquitin ligases. Read More

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http://dx.doi.org/10.15252/embj.2019101633DOI Listing
February 2019

Length doesn't matter-telomere damage triggers cellular senescence in the ageing heart.

Authors:
Thomas Brand

EMBO J 2019 Feb 15. Epub 2019 Feb 15.

Developmental Dynamics, National Heart and Lung Institute (NHLI), Imperial College London, London, UK.

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http://dx.doi.org/10.15252/embj.2019101571DOI Listing
February 2019

A multifaceted small RNA modulates gene expression upon glucose limitation in .

EMBO J 2019 Feb 13. Epub 2019 Feb 13.

Architecture et Réactivité de l'ARN, CNRS, Université de Strasbourg, Strasbourg, France

Pathogenic bacteria must rapidly adapt to ever-changing environmental signals resulting in metabolism remodeling. The carbon catabolite repression, mediated by the catabolite control protein A (CcpA), is used to express genes involved in utilization and metabolism of the preferred carbon source. Here, we have identified RsaI as a CcpA-repressed small non-coding RNA that is inhibited by high glucose concentrations. Read More

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http://dx.doi.org/10.15252/embj.201899363DOI Listing
February 2019

Nuclear import of the DSCAM-cytoplasmic domain drives signaling capable of inhibiting synapse formation.

EMBO J 2019 Feb 11. Epub 2019 Feb 11.

VIB Center for Brain & Disease Research, Leuven, Belgium

DSCAM and DSCAML1 are immunoglobulin and cell adhesion-type receptors serving important neurodevelopmental functions including control of axon growth, branching, neurite self-avoidance, and neuronal cell death. The signal transduction mechanisms or effectors of DSCAM receptors, however, remain poorly characterized. We used a human ORFeome library to perform a high-throughput screen in mammalian cells and identified novel cytoplasmic signaling effector candidates including the Down syndrome kinase Dyrk1a, STAT3, USP21, and SH2D2A. Read More

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http://dx.doi.org/10.15252/embj.201899669DOI Listing
February 2019
1 Read

Length-independent telomere damage drives post-mitotic cardiomyocyte senescence.

EMBO J 2019 Feb 8. Epub 2019 Feb 8.

Ageing Research Laboratories, Institute for Ageing, Newcastle University, Newcastle upon Tyne, UK

Ageing is the biggest risk factor for cardiovascular disease. Cellular senescence, a process driven in part by telomere shortening, has been implicated in age-related tissue dysfunction. Here, we address the question of how senescence is induced in rarely dividing/post-mitotic cardiomyocytes and investigate whether clearance of senescent cells attenuates age-related cardiac dysfunction. Read More

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http://dx.doi.org/10.15252/embj.2018100492DOI Listing
February 2019
1 Read

Defining multistep cell fate decision pathways during pancreatic development at single-cell resolution.

EMBO J 2019 Feb 8. Epub 2019 Feb 8.

Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China

The generation of terminally differentiated cell lineages during organogenesis requires multiple, coordinated cell fate choice steps. However, this process has not been clearly delineated, especially in complex solid organs such as the pancreas. Here, we performed single-cell RNA-sequencing in pancreatic cells sorted from multiple genetically modified reporter mouse strains at embryonic stages E9. Read More

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http://dx.doi.org/10.15252/embj.2018100164DOI Listing
February 2019

Endophilin-A regulates presynaptic Ca influx and synaptic vesicle recycling in auditory hair cells.

EMBO J 2019 Feb 7. Epub 2019 Feb 7.

Collaborative Research Center 889, University of Göttingen, Göttingen, Germany

Ribbon synapses of cochlear inner hair cells (IHCs) operate with high rates of neurotransmission; yet, the molecular regulation of synaptic vesicle (SV) recycling at these synapses remains poorly understood. Here, we studied the role of endophilins-A1-3, endocytic adaptors with curvature-sensing and curvature-generating properties, in mouse IHCs. Single-cell RT-PCR indicated the expression of endophilins-A1-3 in IHCs, and immunoblotting confirmed the presence of endophilin-A1 and endophilin-A2 in the cochlea. Read More

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http://dx.doi.org/10.15252/embj.2018100116DOI Listing
February 2019

Cas9 slide-and-seek for phage defense and genome engineering.

EMBO J 2019 Feb 7;38(4). Epub 2019 Feb 7.

Department of Microbiology and Immunology, Montana State University, Bozeman, MT, USA.

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http://dx.doi.org/10.15252/embj.2019101474DOI Listing
February 2019

EZH2 cooperates with gain-of-function p53 mutants to promote cancer growth and metastasis.

EMBO J 2019 Feb 5. Epub 2019 Feb 5.

Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA

In light of the increasing number of identified cancer-driven gain-of-function (GOF) mutants of p53, it is important to define a common mechanism to systematically target several mutants, rather than developing strategies tailored to inhibit each mutant individually. Here, using RNA immunoprecipitation-sequencing (RIP-seq), we identified the Polycomb-group histone methyltransferase EZH2 as a p53 mRNA-binding protein. EZH2 bound to an internal ribosome entry site (IRES) in the 5'UTR of p53 mRNA and enhanced p53 protein translation in a methyltransferase-independent manner. Read More

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http://emboj.embopress.org/lookup/doi/10.15252/embj.20189959
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http://dx.doi.org/10.15252/embj.201899599DOI Listing
February 2019
2 Reads

An airway organoid is forever.

EMBO J 2019 Feb 4;38(4). Epub 2019 Feb 4.

Stem Cell Program and Divisions of Hematology/Oncology and Pulmonary & Respiratory Diseases, Boston Children's Hospital, Boston, MA, USA.

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http://dx.doi.org/10.15252/embj.2019101526DOI Listing
February 2019

The herpesviral antagonist m152 reveals differential activation of STING-dependent IRF and NF-κB signaling and STING's dual role during MCMV infection.

EMBO J 2019 Jan 29. Epub 2019 Jan 29.

Viral Immune Modulation Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany

Cytomegaloviruses (CMVs) are master manipulators of the host immune response. Here, we reveal that the murine CMV (MCMV) protein m152 specifically targets the type I interferon (IFN) response by binding to stimulator of interferon genes (STING), thereby delaying its trafficking to the Golgi compartment from where STING initiates type I IFN signaling. Infection with an MCMV lacking m152 induced elevated type I IFN responses and this leads to reduced viral transcript levels both and This effect is ameliorated in the absence of STING Interestingly, while m152 inhibits STING-mediated IRF signaling, it did not affect STING-mediated NF-κB signaling. Read More

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http://dx.doi.org/10.15252/embj.2018100983DOI Listing
January 2019

Abnormal TDP-43 function impairs activity-dependent BDNF secretion, synaptic plasticity, and cognitive behavior through altered Sortilin splicing.

EMBO J 2019 Jan 28. Epub 2019 Jan 28.

Department of Physiology, National University of Singapore, Singapore City, Singapore

Aberrant function of the RNA-binding protein TDP-43 has been causally linked to multiple neurodegenerative diseases. Due to its large number of targets, the mechanisms through which TDP-43 malfunction cause disease are unclear. Here, we report that knockdown, aggregation, or disease-associated mutation of TDP-43 all impair intracellular sorting and activity-dependent secretion of the neurotrophin brain-derived neurotrophic factor (BDNF) through altered splicing of the trafficking receptor Sortilin. 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.2018100989DOI Listing
January 2019
5 Reads

The pseudokinase TRIB1 toggles an intramolecular switch to regulate COP1 nuclear export.

EMBO J 2019 Feb 28;38(4). Epub 2019 Jan 28.

Cardiovascular Research Institute, University of California-San Francisco, San Francisco, CA, USA

COP1 is a highly conserved ubiquitin ligase that regulates diverse cellular processes in plants and metazoans. Tribbles pseudokinases, which only exist in metazoans, act as scaffolds that interact with COP1 and its substrates to facilitate ubiquitination. Here, we report that, in addition to this scaffolding role, TRIB1 promotes nuclear localization of COP1 by disrupting an intramolecular interaction between the WD40 domain and a previously uncharacterized regulatory site within COP1. Read More

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http://emboj.embopress.org/lookup/doi/10.15252/embj.20189970
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http://dx.doi.org/10.15252/embj.201899708DOI Listing
February 2019
2 Reads

Getting into shape: tissue tension drives oriented cell divisions during organogenesis.

EMBO J 2019 Feb 24;38(3). Epub 2019 Jan 24.

Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

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http://dx.doi.org/10.15252/embj.2018101246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356058PMC
February 2019
1 Read

Long-term expanding human airway organoids for disease modeling.

EMBO J 2019 Feb 14;38(4). Epub 2019 Jan 14.

Oncode Institute, Hubrecht Institute-KNAW and UMC Utrecht, Utrecht, The Netherlands

Organoids are self-organizing 3D structures grown from stem cells that recapitulate essential aspects of organ structure and function. Here, we describe a method to establish long-term-expanding human airway organoids from broncho-alveolar resections or lavage material. The pseudostratified airway organoids consist of basal cells, functional multi-ciliated cells, mucus-producing secretory cells, and CC10-secreting club cells. Read More

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http://dx.doi.org/10.15252/embj.2018100300DOI Listing
February 2019
6 Reads
10.434 Impact Factor

Revealing the Superpowers of PrimPol: rescuing replicating microsatellites.

EMBO J 2019 Feb 14;38(3). Epub 2019 Jan 14.

The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.

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http://dx.doi.org/10.15252/embj.2018101298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356056PMC
February 2019
1 Read

Bacterial killing by complement requires membrane attack complex formation via surface-bound C5 convertases.

EMBO J 2019 Feb 14;38(4). Epub 2019 Jan 14.

Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

The immune system kills bacteria by the formation of lytic membrane attack complexes (MACs), triggered when complement enzymes cleave C5. At present, it is not understood how the MAC perturbs the composite cell envelope of Gram-negative bacteria. Here, we show that the role of C5 convertase enzymes in MAC assembly extends beyond the cleavage of C5 into the MAC precursor C5b. Read More

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http://dx.doi.org/10.15252/embj.201899852DOI Listing
February 2019
1 Read

An increase in neural stem cells and olfactory bulb adult neurogenesis improves discrimination of highly similar odorants.

EMBO J 2019 Jan 14. Epub 2019 Jan 14.

CRTD Center for Regenerative Therapies Dresden, School of Medicine, TU Dresden, Dresden, Germany

Adult neurogenesis is involved in cognitive performance but studies that manipulated this process to improve brain function are scarce. Here, we characterized a genetic mouse model in which neural stem cells (NSC) of the subventricular zone (SVZ) were temporarily expanded by conditional expression of the cell cycle regulators Cdk4/cyclinD1, thus increasing neurogenesis. We found that supernumerary neurons matured and integrated in the olfactory bulb similarly to physiologically generated newborn neurons displaying a correct expression of molecular markers, morphology and electrophysiological activity. Read More

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http://dx.doi.org/10.15252/embj.201798791DOI Listing
January 2019
1 Read

Localized incorporation of outer membrane components in the pathogen .

EMBO J 2019 Jan 11. Epub 2019 Jan 11.

Research Unit in Biology of Microorganisms (URBM), Narilis University of Namur (UNamur), Namur, Belgium

The zoonotic pathogen is part of the Rhizobiales, which are alpha-proteobacteria displaying unipolar growth. Here, we show that this bacterium exhibits heterogeneity in its outer membrane composition, with clusters of rough lipopolysaccharide co-localizing with the essential outer membrane porin Omp2b, which is proposed to allow facilitated diffusion of solutes through the porin. We also show that the major outer membrane protein Omp25 and peptidoglycan are incorporated at the new pole and the division site, the expected growth sites. Read More

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http://dx.doi.org/10.15252/embj.2018100323DOI Listing
January 2019
1 Read

Atoh1 secretory progenitors possess renewal capacity independent of Lgr5 cells during colonic regeneration.

EMBO J 2019 Feb 11;38(4). Epub 2019 Jan 11.

Department of Medicine, University of Western Ontario, London, ON, Canada

During homeostasis, the colonic epithelium is replenished every 3-5 days by rapidly cycling stem cells. However, various insults can lead to depletion of stem cells, and colonic epithelium can be regenerated from negative cells. While studies in the small intestine have addressed the lineage identity of the negative regenerative cell population, in the colon this question has remained unanswered. Read More

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http://dx.doi.org/10.15252/embj.201899984DOI Listing
February 2019
1 Read

Transcriptional regulation of normal human mammary cell heterogeneity and its perturbation in breast cancer.

EMBO J 2019 Jan 11. Epub 2019 Jan 11.

Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada

The mammary gland in adult women consists of biologically distinct cell types that differ in their surface phenotypes. Isolation and molecular characterization of these subpopulations of mammary cells have provided extensive insights into their different transcriptional programs and regulation. This information is now serving as a baseline for interpreting the heterogeneous features of human breast cancers. Read More

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http://dx.doi.org/10.15252/embj.2018100330DOI Listing
January 2019
1 Read

Clustering of Tau fibrils impairs the synaptic composition of α3-Na/K-ATPase and AMPA receptors.

EMBO J 2019 Feb 10;38(3). Epub 2019 Jan 10.

CEA, Institut François Jacob (MIRcen) and CNRS Laboratory of Neurodegenerative Diseases (UMR9199), Fontenay-aux-Roses, France

Tau assemblies have prion-like properties: they propagate from one neuron to another and amplify by seeding the aggregation of endogenous Tau. Although key in prion-like propagation, the binding of exogenous Tau assemblies to the plasma membrane of naïve neurons is not understood. We report that fibrillar Tau forms clusters at the plasma membrane following lateral diffusion. Read More

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http://dx.doi.org/10.15252/embj.201899871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356061PMC
February 2019
1 Read
10.434 Impact Factor

Beclin1-driven autophagy modulates the inflammatory response of microglia via NLRP3.

EMBO J 2019 Feb 7;38(4). Epub 2019 Jan 7.

Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.

Alzheimer's disease is characterized not only by extracellular amyloid plaques and neurofibrillary tangles, but also by microglia-mediated neuroinflammation. Recently, autophagy has been linked to the regulation of the inflammatory response. Thus, we investigated how an impairment of autophagy mediated by BECN1/Beclin1 reduction, as described in Alzheimer's disease patients, would influence cytokine production of microglia. Read More

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http://dx.doi.org/10.15252/embj.201899430DOI Listing
February 2019
1 Read

The nature of the biological material and the irreproducibility problem in biomedical research.

EMBO J 2019 Feb 7;38(4). Epub 2019 Jan 7.

Biomedical Division, The Institute of Molecular Biology and Biotechnology, FORTH-ITE, Heraklion, Crete, Greece.

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http://dx.doi.org/10.15252/embj.2018101011DOI Listing
February 2019
4 Reads

A dual role for cell plate-associated PI4Kβ in endocytosis and phragmoplast dynamics during plant somatic cytokinesis.

EMBO J 2019 Feb 7;38(4). Epub 2019 Jan 7.

Department of Cellular Biochemistry, Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany

Plant cytokinesis involves membrane trafficking and cytoskeletal rearrangements. Here, we report that the phosphoinositide kinases PI4Kβ1 and PI4Kβ2 integrate these processes in () roots. Cytokinetic defects of an double mutant are accompanied by defects in membrane trafficking. Read More

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http://dx.doi.org/10.15252/embj.2018100303DOI Listing
February 2019
9 Reads

A -acting bidirectional transcription switch controls sexual dimorphism in the liverwort.

EMBO J 2019 Jan 4. Epub 2019 Jan 4.

Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Nara, Japan

Plant life cycles alternate between haploid gametophytes and diploid sporophytes. While regulatory factors determining male and female sexual morphologies have been identified for sporophytic reproductive organs, such as stamens and pistils of angiosperms, those regulating sex-specific traits in the haploid gametophytes that produce male and female gametes and hence are central to plant sexual reproduction are poorly understood. Here, we identified a MYB-type transcription factor, MpFGMYB, as a key regulator of female sexual differentiation in the haploid-dominant dioicous liverwort, MpFGMYB is specifically expressed in females and its loss resulted in female-to-male sex conversion. Read More

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http://dx.doi.org/10.15252/embj.2018100240DOI Listing
January 2019
7 Reads

Frozen-hydrated chromatin from metaphase chromosomes has an interdigitated multilayer structure.

EMBO J 2019 Jan 4. Epub 2019 Jan 4.

Departament de Bioquímica i Biologia Molecular, Facultat de Biociències, Universitat Autònoma de Barcelona, Barcelona, Spain

Cryo-electron tomography and small-angle X-ray scattering were used to investigate the chromatin folding in metaphase chromosomes. The tomographic 3D reconstructions show that frozen-hydrated chromatin emanated from chromosomes is planar and forms multilayered plates. The layer thickness was measured accounting for the contrast transfer function fringes at the plate edges, yielding a width of ~ 7. Read More

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http://dx.doi.org/10.15252/embj.201899769DOI Listing
January 2019
1 Read

Collided ribosomes form a unique structural interface to induce Hel2-driven quality control pathways.

EMBO J 2019 Jan 4. Epub 2019 Jan 4.

Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan

Ribosome stalling triggers quality control pathways targeting the mRNA (NGD: no-go decay) and the nascent polypeptide (RQC: ribosome-associated quality control). RQC requires Hel2-dependent uS10 ubiquitination and the RQT complex in yeast. Here, we report that Hel2-dependent uS10 ubiquitination and Slh1/Rqt2 are crucial for RQC and NGD induction within a di-ribosome (disome) unit, which consists of the leading stalled ribosome and the following colliding ribosome. Read More

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http://dx.doi.org/10.15252/embj.2018100276DOI Listing
January 2019
1 Read

Structure and transformation of bacteriophage A511 baseplate and tail upon infection of  cells.

EMBO J 2019 Feb 2;38(3). Epub 2019 Jan 2.

Laboratory of Structural Biology and Biophysics, School of Basic Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

Contractile injection systems (bacteriophage tails, type VI secretions system, R-type pyocins, etc.) utilize a rigid tube/contractile sheath assembly for breaching the envelope of bacterial and eukaryotic cells. Among contractile injection systems, bacteriophages that infect Gram-positive bacteria represent the least understood members. Read More

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http://dx.doi.org/10.15252/embj.201899455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356063PMC
February 2019
1 Read

CDK phosphorylation of M18BP1 promotes its metaphase centromere localization.

EMBO J 2019 Feb 2;38(4). Epub 2019 Jan 2.

Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA

Chromosome segregation requires the centromere, the site on chromosomes where kinetochores assemble in mitosis to attach chromosomes to the mitotic spindle. Centromere identity is defined epigenetically by the presence of nucleosomes containing the histone H3 variant CENP-A. New CENP-A nucleosome assembly occurs at the centromere every cell cycle during G1, but how CENP-A nucleosome assembly is spatially and temporally restricted remains poorly understood. Read More

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http://emboj.embopress.org/lookup/doi/10.15252/embj.20181000
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http://dx.doi.org/10.15252/embj.2018100093DOI Listing
February 2019
5 Reads

A mitochondrial FUNDC1/HSC70 interaction organizes the proteostatic stress response at the risk of cell morbidity.

EMBO J 2019 Feb 27;38(3). Epub 2018 Dec 27.

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China

Both protein quality and mitochondrial quality are vital for the cellular activity, and impaired proteostasis and mitochondrial dysfunction are common etiologies of aging and age-related disorders. Here, we report that the mitochondrial outer membrane protein FUNDC1 interacts with the chaperone HSC70 to promote the mitochondrial translocation of unfolded cytosolic proteins for degradation by LONP1 or for formation of non-aggresomal mitochondrion-associated protein aggregates (MAPAs) upon proteasome inhibition in cultured human cells. Integrative approaches including csCLEM, Apex, and biochemical analysis reveal that MAPAs contain ubiquitinated cytosolic proteins, autophagy receptor p62, and mitochondrial proteins. Read More

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http://emboj.embopress.org/lookup/doi/10.15252/embj.20179878
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http://dx.doi.org/10.15252/embj.201798786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356068PMC
February 2019
20 Reads
10.434 Impact Factor

TFEB controls vascular development by regulating the proliferation of endothelial cells.

EMBO J 2019 Feb 27;38(3). Epub 2018 Dec 27.

Department of Oncology, University of Turin, Candiolo, Italy

Transcription factor TFEB is thought to control cellular functions-including in the vascular bed-primarily via regulation of lysosomal biogenesis and autophagic flux. Here, we report that TFEB also orchestrates a non-canonical program that controls the cell cycle/VEGFR2 pathway in the developing vasculature. In endothelial cells, TFEB depletion halts proliferation at the G1-S transition by inhibiting the CDK4/Rb pathway. Read More

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http://dx.doi.org/10.15252/embj.201798250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356157PMC
February 2019
1 Read

CFTR is not a gluten lover either.

EMBO J 2019 Jan 20;38(2). Epub 2018 Dec 20.

Epithelial Signaling and Transport Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.

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http://dx.doi.org/10.15252/embj.2018101200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331715PMC
January 2019
1 Read

CRISPR/Cas9 searches for a protospacer adjacent motif by lateral diffusion.

EMBO J 2019 Feb 20;38(4). Epub 2018 Dec 20.

Department of BioNanoScience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands

The Streptococcus pyogenes CRISPR/Cas9 (SpCas9) nuclease has been widely applied in genetic engineering. Despite its importance in genome editing, aspects of the precise molecular mechanism of Cas9 activity remain ambiguous. In particular, because of the lack of a method with high spatio-temporal resolution, transient interactions between Cas9 and DNA could not be reliably investigated. Read More

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http://dx.doi.org/10.15252/embj.201899466DOI Listing
February 2019
1 Read

A novel form of JARID2 is required for differentiation in lineage-committed cells.

EMBO J 2019 Feb 20;38(3). Epub 2018 Dec 20.

School of Biosciences, University of Birmingham, Birmingham, UK

Polycomb repressive complex-2 (PRC2) is a group of proteins that play an important role during development and in cell differentiation. PRC2 is a histone-modifying complex that catalyses methylation of lysine 27 of histone H3 (H3K27me3) at differentiation genes leading to their transcriptional repression. JARID2 is a co-factor of PRC2 and is important for targeting PRC2 to chromatin. Read More

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http://emboj.embopress.org/lookup/doi/10.15252/embj.20179844
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http://dx.doi.org/10.15252/embj.201798449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356158PMC
February 2019
4 Reads

Parkin inhibits BAK and BAX apoptotic function by distinct mechanisms during mitophagy.

EMBO J 2019 Jan 20;38(2). Epub 2018 Dec 20.

Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Vic., Australia

The E3 ubiquitin ligase Parkin is a key effector of the removal of damaged mitochondria by mitophagy. Parkin determines cell fate in response to mitochondrial damage, with its loss promoting early onset Parkinson's disease and potentially also cancer progression. Controlling a cell's apoptotic response is essential to co-ordinate the removal of damaged mitochondria. Read More

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http://dx.doi.org/10.15252/embj.201899916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331729PMC
January 2019
1 Read

Fat-fated microglial dysfunction.

EMBO J 2019 Jan 19;38(2). Epub 2018 Dec 19.

Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.

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http://dx.doi.org/10.15252/embj.2018101176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331718PMC
January 2019
1 Read

Avidity-driven polarity establishment via multivalent lipid-GTPase module interactions.

EMBO J 2019 Feb 17;38(3). Epub 2018 Dec 17.

CNRS, UMR 5095, European Institute of Chemistry and Biology, University of Bordeaux, Pessac, France

While Rho GTPases are indispensible regulators of cellular polarity, the mechanisms underlying their anisotropic activation at membranes have been elusive. Using the budding yeast Cdc42 GTPase module, which includes a guanine nucleotide exchange factor (GEF) Cdc24 and the scaffold Bem1, we find that avidity generated via multivalent anionic lipid interactions is a critical mechanistic constituent of polarity establishment. We identify basic cluster (BC) motifs in Bem1 that drive the interaction of the scaffold-GEF complex with anionic lipids at the cell pole. Read More

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http://dx.doi.org/10.15252/embj.201899652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356062PMC
February 2019
1 Read

A selective ER-phagy exerts procollagen quality control via a Calnexin-FAM134B complex.

EMBO J 2019 Jan 17;38(2). Epub 2018 Dec 17.

Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy

Autophagy is a cytosolic quality control process that recognizes substrates through receptor-mediated mechanisms. Procollagens, the most abundant gene products in Metazoa, are synthesized in the endoplasmic reticulum (ER), and a fraction that fails to attain the native structure is cleared by autophagy. However, how autophagy selectively recognizes misfolded procollagens in the ER lumen is still unknown. Read More

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http://emboj.embopress.org/lookup/doi/10.15252/embj.20189984
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http://dx.doi.org/10.15252/embj.201899847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331724PMC
January 2019
23 Reads

RagC phosphorylation autoregulates mTOR complex 1.

EMBO J 2019 Feb 14;38(3). Epub 2018 Dec 14.

School of Life and Environmental Sciences, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia

The mechanistic (or mammalian) target of rapamycin complex 1 (mTORC1) controls cell growth, proliferation, and metabolism in response to diverse stimuli. Two major parallel pathways are implicated in mTORC1 regulation including a growth factor-responsive pathway mediated via TSC2/Rheb and an amino acid-responsive pathway mediated via the Rag GTPases. Here, we identify and characterize three highly conserved growth factor-responsive phosphorylation sites on RagC, a component of the Rag heterodimer, implicating cross talk between amino acid and growth factor-mediated regulation of mTORC1. Read More

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http://dx.doi.org/10.15252/embj.201899548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356064PMC
February 2019
2 Reads

Let it RE:IN: integrating experimental observations to predict pluripotency network behaviour.

EMBO J 2019 Jan 13;38(1). Epub 2018 Dec 13.

Department of Anatomy and Developmental Biology, Monash University, Clayton, Vic., Australia.

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http://dx.doi.org/10.15252/embj.2018101133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315288PMC
January 2019
1 Read

SUMOning the base excision repair machinery for differentiation.

EMBO J 2019 Jan 13;38(1). Epub 2018 Dec 13.

Departments of Internal Medicine, Molecular Genetics and Microbiology, University of New Mexico Comprehensive Cancer Center, University of New Mexico School of Medicine, Albuquerque, NM, USA.

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http://dx.doi.org/10.15252/embj.2018101147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315293PMC
January 2019
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SUMOylation coordinates BERosome assembly in active DNA demethylation during cell differentiation.

EMBO J 2019 Jan 6;38(1). Epub 2018 Dec 6.

Department of Biomedicine, University of Basel, Basel, Switzerland

During active DNA demethylation, 5-methylcytosine (5mC) is oxidized by TET proteins to 5-formyl-/5-carboxylcytosine (5fC/5caC) for replacement by unmethylated C by TDG-initiated DNA base excision repair (BER). Base excision generates fragile abasic sites (AP-sites) in DNA and has to be coordinated with subsequent repair steps to limit accumulation of genome destabilizing secondary DNA lesions. Here, we show that 5fC/5caC is generated at a high rate in genomes of differentiating mouse embryonic stem cells and that SUMOylation and the BER protein XRCC1 play critical roles in orchestrating TDG-initiated BER of these lesions. Read More

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http://dx.doi.org/10.15252/embj.201899242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315294PMC
January 2019
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Prominin-1 controls stem cell activation by orchestrating ciliary dynamics.

EMBO J 2019 Jan 6;38(2). Epub 2018 Dec 6.

Peninsula Dental School, University of Plymouth, Plymouth, UK

Proper temporal and spatial activation of stem cells relies on highly coordinated cell signaling. The primary cilium is the sensory organelle that is responsible for transmitting extracellular signals into a cell. Primary cilium size, architecture, and assembly-disassembly dynamics are under rigid cell cycle-dependent control. Read More

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http://emboj.embopress.org/lookup/doi/10.15252/embj.20189984
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http://dx.doi.org/10.15252/embj.201899845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331727PMC
January 2019
9 Reads

Disease-associated tau impairs mitophagy by inhibiting Parkin translocation to mitochondria.

EMBO J 2019 Feb 11;38(3). Epub 2018 Dec 11.

Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia

Accumulation of the protein tau characterises Alzheimer's disease and other tauopathies, including familial forms of frontotemporal dementia (FTD) that carry pathogenic tau mutations. Another hallmark feature of these diseases is the accumulation of dysfunctional mitochondria. Although disease-associated tau is known to impair several aspects of mitochondrial function, it is still unclear whether it also directly impinges on mitochondrial quality control, specifically Parkin-dependent mitophagy. Read More

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http://dx.doi.org/10.15252/embj.201899360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356067PMC
February 2019
2 Reads