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EMBO Journal

Alex B Wang, Ying V Zhang, Tudorita Tumbar
Cell proliferation is essential to rapid tissue growth and repair, but can result in replication-associated genome damage. Here, we implicate the transcription factor Gata6 in adult mouse hair follicle regeneration where it controls the renewal of rapidly proliferating epithelial (matrix) progenitors and hence the extent of production of terminally differentiated lineages. We find that Gata6 protects against DNA damage associated with proliferation, thus preventing cell cycle arrest and apoptosis. Furthermore, we show that in vivo Gata6 stimulates EDA-receptor signaling adaptor Edaradd level and NF-κB pathway activation, known to be important for DNA damage repair and stress response in general and for hair follicle growth in particular...
December 1, 2016: EMBO Journal
Bernd Pulverer
No abstract text is available yet for this article.
December 1, 2016: EMBO Journal
Marta Seczynska, Ivan Dikic
No abstract text is available yet for this article.
November 28, 2016: EMBO Journal
Veijo T Salo, Ilya Belevich, Shiqian Li, Leena Karhinen, Helena Vihinen, Corinne Vigouroux, Jocelyne Magré, Christoph Thiele, Maarit Hölttä-Vuori, Eija Jokitalo, Elina Ikonen
Seipin is an endoplasmic reticulum (ER) membrane protein implicated in lipid droplet (LD) biogenesis and mutated in severe congenital lipodystrophy (BSCL2). Here, we show that seipin is stably associated with nascent ER-LD contacts in human cells, typically via one mobile focal point per LD Seipin appears critical for such contacts since ER-LD contacts were completely missing or morphologically aberrant in seipin knockout and BSCL2 patient cells. In parallel, LD mobility was increased and protein delivery from the ER to LDs to promote LD growth was decreased...
November 22, 2016: EMBO Journal
Mai Kanke, Eri Tahara, Pim J Huis In't Veld, Tomoko Nishiyama
Cohesin is a ring-shaped protein complex that plays a crucial role in sister chromatid cohesion and gene expression. The dynamic association of cohesin with chromatin is essential for these functions. However, the exact nature of cohesin dynamics, particularly cohesin translocation, remains unclear. We evaluated the dynamics of individual cohesin molecules on DNA and found that the cohesin core complex possesses an intrinsic ability to traverse DNA in an adenosine triphosphatase (ATPase)-dependent manner. Translocation ability is suppressed in the presence of Wapl-Pds5 and Sororin; this suppression is alleviated by the acetylation of cohesin and the action of mitotic kinases...
November 21, 2016: EMBO Journal
Joseph E Pick, Latika Khatri, Matheus F Sathler, Edward B Ziff
mGluR long-term depression (mGluR-LTD) is a form of synaptic plasticity induced at excitatory synapses by metabotropic glutamate receptors (mGluRs). mGluR-LTD reduces synaptic strength and is relevant to learning and memory, autism, and sensitization to cocaine; however, the mechanism is not known. Here we show that activation of Group I mGluRs in medium spiny neurons induces trafficking of GluA2 from the endoplasmic reticulum (ER) to the synapse by enhancing GluA2 binding to essential COPII vesicle proteins, Sec23 and Sec13...
November 17, 2016: EMBO Journal
Yuxin Wang, Jing Nan, Belinda Willard, Xin Wang, Jinbo Yang, George R Stark
The transcription factor ISGF3, comprised of IRF9 and tyrosine-phosphorylated STATs 1 and 2, transmits the signal from the type I interferon receptor to the genome. We have discovered a novel phosphorylation of STAT2 on T387 that negatively regulates this response. In most untreated cell types, the majority of STAT2 is phosphorylated on T387 constitutively. In response to interferon-β, the T387A mutant of STAT2 is much more effective than wild-type STAT2 in mediating the expression of many interferon-stimulated genes, in protecting cells against virus infection, and in inhibiting cell growth...
November 16, 2016: EMBO Journal
María Teresa Villoria, Facundo Ramos, Encarnación Dueñas, Peter Faull, Pedro Rodríguez Cutillas, Andrés Clemente-Blanco
Cells are constantly threatened by multiple sources of genotoxic stress that cause DNA damage. To maintain genome integrity, cells have developed a coordinated signalling network called DNA damage response (DDR). While multiple kinases have been thoroughly studied during DDR activation, the role of protein dephosphorylation in the damage response remains elusive. Here, we show that the phosphatase Cdc14 is essential to fulfil recombinational DNA repair in budding yeast. After DNA double-strand break (DSB) generation, Cdc14 is transiently released from the nucleolus and activated...
November 16, 2016: EMBO Journal
Svetlana Ulyanchenko, Kim B Jensen
No abstract text is available yet for this article.
November 14, 2016: EMBO Journal
Matteo Villa, Manolis Gialitakis, Mauro Tolaini, Helena Ahlfors, Colin J Henderson, C Roland Wolf, Robert Brink, Brigitta Stockinger
The aryl hydrocarbon receptor (AhR), a transcription factor known for mediating xenobiotic toxicity, is expressed in B cells, which are known targets for environmental pollutants. However, it is unclear what the physiological functions of AhR in B cells are. We show here that expression of Ahr in B cells is up-regulated upon B-cell receptor (BCR) engagement and IL-4 treatment. Addition of a natural ligand of AhR, FICZ, induces AhR translocation to the nucleus and transcription of the AhR target gene Cyp1a1, showing that the AhR pathway is functional in B cells...
November 14, 2016: EMBO Journal
Shafagh A Waters, Sean P McAteer, Grzegorz Kudla, Ignatius Pang, Nandan P Deshpande, Timothy G Amos, Kai Wen Leong, Marc R Wilkins, Richard Strugnell, David L Gally, David Tollervey, Jai J Tree
RNA sequencing studies have identified hundreds of non-coding RNAs in bacteria, including regulatory small RNA (sRNA). However, our understanding of sRNA function has lagged behind their identification due to a lack of tools for the high-throughput analysis of RNA-RNA interactions in bacteria. Here we demonstrate that in vivo sRNA-mRNA duplexes can be recovered using UV-crosslinking, ligation and sequencing of hybrids (CLASH). Many sRNAs recruit the endoribonuclease, RNase E, to facilitate processing of mRNAs...
November 11, 2016: EMBO Journal
Amayra Hernández-Vega, María Marsal, Philippe-Alexandre Pouille, Sébastien Tosi, Julien Colombelli, Tomás Luque, Daniel Navajas, Ignacio Pagonabarraga, Enrique Martín-Blanco
The principles underlying the biomechanics of morphogenesis are largely unknown. Epiboly is an essential embryonic event in which three tissues coordinate to direct the expansion of the blastoderm. How and where forces are generated during epiboly, and how these are globally coupled remains elusive. Here we developed a method, hydrodynamic regression (HR), to infer 3D pressure fields, mechanical power, and cortical surface tension profiles. HR is based on velocity measurements retrieved from 2D+T microscopy and their hydrodynamic modeling...
November 9, 2016: EMBO Journal
Ilgiz A Mufazalov, Carsten Schelmbauer, Tommy Regen, Janina Kuschmann, Florian Wanke, Laureen A Gabriel, Judith Hauptmann, Werner Müller, Emmanuel Pinteaux, Florian C Kurschus, Ari Waisman
Interleukin-1 (IL-1) is implicated in numerous pathologies, including multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). However, the exact mechanism by which IL-1 is involved in the generation of pathogenic T cells and in disease development remains largely unknown. We found that following EAE induction, pertussis toxin administration leads to IL-1 receptor type 1 (IL-1R1)-dependent IL-1β expression by myeloid cells in the draining lymph nodes. This myeloid-derived IL-1β did not vitally contribute to the generation and plasticity of Th17 cells, but rather promoted the expansion of a GM-CSF(+) Th17 cell subset, thereby enhancing its encephalitogenic potential...
November 8, 2016: EMBO Journal
Iain F Davidson, Daniela Goetz, Maciej P Zaczek, Maxim I Molodtsov, Pim J Huis In 't Veld, Florian Weissmann, Gabriele Litos, David A Cisneros, Maria Ocampo-Hafalla, Rene Ladurner, Frank Uhlmann, Alipasha Vaziri, Jan-Michael Peters
The spatial organization, correct expression, repair, and segregation of eukaryotic genomes depend on cohesin, ring-shaped protein complexes that are thought to function by entrapping DNA It has been proposed that cohesin is recruited to specific genomic locations from distal loading sites by an unknown mechanism, which depends on transcription, and it has been speculated that cohesin movements along DNA could create three-dimensional genomic organization by loop extrusion. However, whether cohesin can translocate along DNA is unknown...
October 31, 2016: EMBO Journal
Rolf Hilgenfeld
No abstract text is available yet for this article.
October 27, 2016: EMBO Journal
Philip Lössl, Michiel van de Waterbeemd, Albert Jr Heck
The emergence of proteomics has led to major technological advances in mass spectrometry (MS). These advancements not only benefitted MS-based high-throughput proteomics but also increased the impact of mass spectrometry on the field of structural and molecular biology. Here, we review how state-of-the-art MS methods, including native MS, top-down protein sequencing, cross-linking-MS, and hydrogen-deuterium exchange-MS, nowadays enable the characterization of biomolecular structures, functions, and interactions...
October 26, 2016: EMBO Journal
Hiroyuki Miyoshi, Kelli L VanDussen, Nicole P Malvin, Stacy H Ryu, Yi Wang, Naomi M Sonnek, Chin-Wen Lai, Thaddeus S Stappenbeck
Adaptive cellular responses are often required during wound repair. Following disruption of the intestinal epithelium, wound-associated epithelial (WAE) cells form the initial barrier over the wound. Our goal was to determine the critical factor that promotes WAE cell differentiation. Using an adaptation of our in vitro primary epithelial cell culture system, we found that prostaglandin E2 (PGE2) signaling through one of its receptors, Ptger4, was sufficient to drive a differentiation state morphologically and transcriptionally similar to in vivo WAE cells...
October 24, 2016: EMBO Journal
Edwige Roy, Zoltan Neufeld, Luca Cerone, Ho Yi Wong, Samantha Hodgson, Jean Livet, Kiarash Khosrotehrani
Interfollicular epidermal (IFE) homeostasis is a major physiological process allowing maintenance of the skin barrier function. Despite progress in our understanding of stem cell populations in different hair follicle compartments, cellular mechanisms of IFE maintenance, in particular, whether a hierarchy of progenitors exists within this compartment, have remained controversial. We here used multicolour lineage tracing with Brainbow transgenic labels activated in the epidermis to track individual keratinocyte clones...
October 21, 2016: EMBO Journal
Paul Ginsparg
No abstract text is available yet for this article.
October 19, 2016: EMBO Journal
Chrisovalantis Papadopoulos, Philipp Kirchner, Monika Bug, Daniel Grum, Lisa Koerver, Nina Schulze, Robert Poehler, Alina Dressler, Sven Fengler, Khalid Arhzaouy, Vanda Lux, Michael Ehrmann, Conrad C Weihl, Hemmo Meyer
Rupture of endosomes and lysosomes is a major cellular stress condition leading to cell death and degeneration. Here, we identified an essential role for the ubiquitin-directed AAA-ATPase, p97, in the clearance of damaged lysosomes by autophagy. Upon damage, p97 translocates to lysosomes and there cooperates with a distinct set of cofactors including UBXD1, PLAA, and the deubiquitinating enzyme YOD1, which we term ELDR components for Endo-Lysosomal Damage Response. Together, they act downstream of K63-linked ubiquitination and p62 recruitment, and selectively remove K48-linked ubiquitin conjugates from a subpopulation of damaged lysosomes to promote autophagosome formation...
October 17, 2016: EMBO Journal
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