The EMBO Journal

Cover image for Vol. 35 Issue 20

Early View (Online Version of Record published before inclusion in an issue)

Online ISSN: 1460-2075


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  1. Resources

    1. A humanized yeast proteasome identifies unique binding modes of inhibitors for the immunosubunit β5i

      Eva M Huber, Wolfgang Heinemeyer, Gerjan de Bruin, Herman S Overkleeft and Michael Groll

      Version of Record online: 27 OCT 2016 | DOI: 10.15252/embj.201695222

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      Engineering of chimeric yeast/mammalian proteasomes allows crystallographic elucidation of the binding modes and specificities of immunoproteasome inhibitors, which are promising anti-inflammatory drug candidates.

  2. Reviews

    1. You have full text access to this OnlineOpen article
      The diverse and expanding role of mass spectrometry in structural and molecular biology

      Philip Lössl, Michiel van de Waterbeemd and Albert JR Heck

      Version of Record online: 26 OCT 2016 | DOI: 10.15252/embj.201694818

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      Starting from a historical perspective, Albert Heck and colleagues showcase how state-of-the-art mass spectrometry approaches have evolved into powerful tools to elucidate structure and function of proteins and protein complexes.

  3. Articles

    1. The MMS22L–TONSL heterodimer directly promotes RAD51-dependent recombination upon replication stress

      Wojciech Piwko, Lucie J Mlejnkova, Karun Mutreja, Lepakshi Ranjha, Diana Stafa, Alexander Smirnov, Mia ML Brodersen, Ralph Zellweger, Andreas Sturzenegger, Pavel Janscak, Massimo Lopes, Matthias Peter and Petr Cejka

      Version of Record online: 26 OCT 2016 | DOI: 10.15252/embj.201593132

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      RAD51-mediated DNA strand exchange at stalled replication forks requires RPA-dependent fork recruitment of MMS22L–TONSL, explaining how this homologous recombination mediator facilitates fork restart.

    2. Prostaglandin E2 promotes intestinal repair through an adaptive cellular response of the epithelium

      Hiroyuki Miyoshi, Kelli L VanDussen, Nicole P Malvin, Stacy H Ryu, Yi Wang, Naomi M Sonnek, Chin-Wen Lai and Thaddeus S Stappenbeck

      Version of Record online: 24 OCT 2016 | DOI: 10.15252/embj.201694660

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      Intestinal wound-associated epithelial (WAE) cells are a transient class of repair cells critical for repair initiation. Prostaglandin PGE2 triggers WAE cell generation in response to injury, acting through its epithelial receptor EP4.

    3. Bimodal behaviour of interfollicular epidermal progenitors regulated by hair follicle position and cycling

      Edwige Roy, Zoltan Neufeld, Luca Cerone, Ho Yi Wong, Samantha Hodgson, Jean Livet and Kiarash Khosrotehrani

      Version of Record online: 21 OCT 2016 | DOI: 10.15252/embj.201693806

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      Transgenic “skinbow” multicolour lineage tracing and mathematical modelling reveal two distinct modes of progenitor cell proliferation, controlled by relative hair follicle position and cycle phase.

    4. CLPP coordinates mitoribosomal assembly through the regulation of ERAL1 levels

      Karolina Szczepanowska, Priyanka Maiti, Alexandra Kukat, Eduard Hofsetz, Hendrik Nolte, Katharina Senft, Christina Becker, Benedetta Ruzzenente, Hue-Tran Hornig-Do, Rolf Wibom, Rudolf J Wiesner, Marcus Krüger and Aleksandra Trifunovic

      Version of Record online: 20 OCT 2016 | DOI: 10.15252/embj.201694253

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      A combination of proteomics and mouse knockout approaches identifies substrates of the mammalian ClpXP protease, showing that it controls mitochondrial homeostasis by ensuring assembly and function of mitochondrial ribosomes.

    5. Mediator binding to UASs is broadly uncoupled from transcription and cooperative with TFIID recruitment to promoters

      Sebastian Grünberg, Steven Henikoff, Steven Hahn and Gabriel E Zentner

      Version of Record online: 20 OCT 2016 | DOI: 10.15252/embj.201695020

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      A high-resolution map of Mediator distribution in the yeast genome shows preferential binding to upstream activating sequences, poor correlation with transcription levels, and a cooperative role for TFIID and Mediator on target genes.

  4. Commentary

    1. Preprint Déjà Vu

      Paul Ginsparg

      Version of Record online: 19 OCT 2016 | DOI: 10.15252/embj.201695531

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      Preprints allow stable archiving and sharing of research findings with minimal delay, complementing peer-reviewed journals. In the physical sciences, preprints are an integral part the scientific process. Here, the initiator of the concept describes why and how preprints can work in biology.

  5. Articles

    1. VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy

      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 and Hemmo Meyer

      Version of Record online: 17 OCT 2016 | DOI: 10.15252/embj.201695148

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      The AAA-ATPase VCP/p97 governs an endolysosomal damage response pathway (ELDR) that ensures survival after lysosomal rupture and promotes autophagic clearance of the damaged organelles.

    2. RKIP and TBK1 form a positive feedback loop to promote type I interferon production in innate immunity

      Meidi Gu, Zhiyong Liu, Rongrong Lai, Si Liu, Wenlong Lin, Chuan Ouyang, Sheng Ye, He Huang and Xiaojian Wang

      Version of Record online: 17 OCT 2016 | DOI: 10.15252/embj.201694060

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      A positive feedback loop involving TBK1 and its substrate RKIP (Raf kinase inhibitory protein) is essential for interferon responses in virus-infected mice.

    3. You have full text access to this OnlineOpen article
      A pH- and ionic strength-dependent conformational change in the neck region regulates DNGR-1 function in dendritic cells

      Pavel Hanč, Oliver Schulz, Hanna Fischbach, Stephen R Martin, Svend Kjær and Caetano Reis e Sousa

      Version of Record online: 17 OCT 2016 | DOI: 10.15252/embj.201694695

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      The dendritic cell receptor for dead cell-associated antigens senses its relocalization from the cell surface through acidic endosomes to facilitate efficient cross-presentation.

    4. You have full text access to this OnlineOpen article
      Chm7 and Heh1 collaborate to link nuclear pore complex quality control with nuclear envelope sealing

      Brant M Webster, David J Thaller, Jens Jäger, Sarah E Ochmann, Sapan Borah and C Patrick Lusk

      Version of Record online: 12 OCT 2016 | DOI: 10.15252/embj.201694574

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      ESCRT protein Chm7 acts with integral inner nuclear membrane proteins Heh1 and Heh2 at sites of nuclear pore complex (NPC) assembly to seal off defective NPCs, thereby protecting nuclear compartmentalization and cell viability.

    5. Hair cell synaptic dysfunction, auditory fatigue and thermal sensitivity in otoferlin Ile515Thr mutants

      Nicola Strenzke, Rituparna Chakrabarti, Hanan Al-Moyed, Alexandra Müller, Gerhard Hoch, Tina Pangrsic, Gulnara Yamanbaeva, Christof Lenz, Kuan-Ting Pan, Elisabeth Auge, Ruth Geiss-Friedlander, Henning Urlaub, Nils Brose, Carolin Wichmann and Ellen Reisinger

      Version of Record online: 11 OCT 2016 | DOI: 10.15252/embj.201694564

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      A mouse model of the human otoferlin Ile515Thr mutation provides insight into auditory synaptopathy at normal temperature and temperature-sensitive deafness in humans carrying this mutation.

    6. Molecular basis for cytoplasmic RNA surveillance by uridylation-triggered decay in Drosophila

      Madalena M Reimão-Pinto, Raphael A Manzenreither, Thomas R Burkard, Pawel Sledz, Martin Jinek, Karl Mechtler and Stefan L Ameres

      Version of Record online: 11 OCT 2016 | DOI: 10.15252/embj.201695164

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      The identification of an enzyme complex degrading aberrant RNA in flies deepens our understanding of cytoplasmic RNA surveillance and sheds light on the emerging role for RNA modifications.

    7. You have full text access to this OnlineOpen article
      MicroRNA-34/449 controls mitotic spindle orientation during mammalian cortex development

      Juan Pablo Fededa, Christopher Esk, Beata Mierzwa, Rugile Stanyte, Shuiqiao Yuan, Huili Zheng, Klaus Ebnet, Wei Yan, Juergen A Knoblich and Daniel W Gerlich

      Version of Record online: 5 OCT 2016 | DOI: 10.15252/embj.201694056

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      A high-throughput imaging screen identifies a set of miRNAs that control mitotic spindle orientation in neuronal progenitors and radial glial cells and whose expression is required for normal cortical development in mouse.

  6. News & Views

    1. Polycomb-dependent control of cell fate in adult tissue

      Pedro Vizán, Malte Beringer and Luciano Di Croce

      Version of Record online: 4 OCT 2016 | DOI: 10.15252/embj.201695694

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      While the contribution from Polycomb complexes in early development has been extensively studied, two papers now show that PRC2 is required for the proper control of cell fate decisions in the adult intestinal epithelium.

    2. Too much to differentiate: aneuploidy promotes proliferation and teratoma formation in embryonic stem cells

      Zuzana Storchová

      Version of Record online: 28 SEP 2016 | DOI: 10.15252/embj.201695486

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      Uneven number of chromosomes has mostly detrimental consequences in eukaryotic somatic cells, including impaired proliferation and DNA replication. In contrast, work published in this issue of The EMBO Journal shows that aneuploid murine ES cells maintain proliferative capacity and induce tumorigenesis in vivo, but are hindered in their differentiation.

  7. Articles

    1. You have full text access to this OnlineOpen article
      The Arabidopsis CERK1-associated kinase PBL27 connects chitin perception to MAPK activation

      Kenta Yamada, Koji Yamaguchi, Tomomi Shirakawa, Hirofumi Nakagami, Akira Mine, Kazuya Ishikawa, Masayuki Fujiwara, Mari Narusaka, Yoshihiro Narusaka, Kazuya Ichimura, Yuka Kobayashi, Hidenori Matsui, Yuko Nomura, Mika Nomoto, Yasuomi Tada, Yoichiro Fukao, Tamo Fukamizo, Kenichi Tsuda, Ken Shirasu, Naoto Shibuya and Tsutomu Kawasaki

      Version of Record online: 27 SEP 2016 | DOI: 10.15252/embj.201694248

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      Chitin receptor CERK1 transmits immune signals to the intracellular MAPK cascade in plants. This occurs via phosphorylation of MAPKKK5 by the CERK1-associated kinase PBL27, providing a missing link between pathogen perception and signaling output.

  8. Reviews

    1. You have full text access to this OnlineOpen article
      Membrane fission by dynamin: what we know and what we need to know

      Bruno Antonny, Christopher Burd, Pietro De Camilli, Elizabeth Chen, Oliver Daumke, Katja Faelber, Marijn Ford, Vadim A Frolov, Adam Frost, Jenny E Hinshaw, Tom Kirchhausen, Michael M Kozlov, Martin Lenz, Harry H Low, Harvey McMahon, Christien Merrifield, Thomas D Pollard, Phillip J Robinson, Aurélien Roux and Sandra Schmid

      Version of Record online: 26 SEP 2016 | DOI: 10.15252/embj.201694613

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      This consensus review summarizes our current understanding of the function of the fission GTPase dynamin and highlights open questions in the field.

  9. News & Views

    1. T-lymphoid progenitors – we know what they are, but know not what they may be

      Lars Bullinger

      Version of Record online: 26 SEP 2016 | DOI: 10.15252/embj.201695613

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      Recent work published in The EMBO Journal yielded new insights into the biology underlying leukemogenesis, presenting evidence that a subgroup of human acute myeloid leukemia (AML) might arise from T-cell progenitors, showing multilineage plasticity potential and transdifferentiation under oncogenic conditions.

  10. Articles

    1. A Golgi rhomboid protease Rbd2 recruits Cdc48 to cleave yeast SREBP

      Jiwon Hwang, Diedre Ribbens, Sumana Raychaudhuri, Leah Cairns, He Gu, Adam Frost, Siniša Urban and Peter J Espenshade

      Version of Record online: 21 SEP 2016 | DOI: 10.15252/embj.201693923

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      Proteolytic activation of the fission yeast sterol-responsive transcriptional regulator requires its sequential ubiquitination and Cdc48-dependent presentation to an intramembrane protease.

    2. Evi1 regulates Notch activation to induce zebrafish hematopoietic stem cell emergence

      Martina Konantz, Elisa Alghisi, Joëlle S Müller, Anna Lenard, Virginie Esain, Kelli J Carroll, Lothar Kanz, Trista E North and Claudia Lengerke

      Version of Record online: 16 SEP 2016 | DOI: 10.15252/embj.201593454

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      A new VEGF-independent pathway triggers Notch-mediated conversion of dorsal aorta endothelial cells into definitive hematopoietic stem cells during embryonic endothelial-to-hematopoietic transition.

    3. You have full text access to this OnlineOpen article
      Molecular requirements of the B-cell antigen receptor for sensing monovalent antigens

      Christoph Volkmann, Naema Brings, Martin Becker, Elias Hobeika, Jianying Yang and Michael Reth

      Version of Record online: 15 SEP 2016 | DOI: 10.15252/embj.201694177

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      Proximity ligation assays reveal that monovalent antigen-binding site ligands are sufficient to induce B-cell receptor conformational changes, promoting downstream intracellular signalling.

    4. You have full text access to this OnlineOpen article
      TDP-43 loss of function inhibits endosomal trafficking and alters trophic signaling in neurons

      Benjamin M Schwenk, Hannelore Hartmann, Alperen Serdaroglu, Martin H Schludi, Daniel Hornburg, Felix Meissner, Denise Orozco, Alessio Colombo, Sabina Tahirovic, Meike Michaelsen, Franziska Schreiber, Simone Haupt, Michael Peitz, Oliver Brüstle, Clemens Küpper, Thomas Klopstock, Markus Otto, Albert C Ludolph, Thomas Arzberger, Peer-Hendrik Kuhn and Dieter Edbauer

      Version of Record online: 12 SEP 2016 | DOI: 10.15252/embj.201694221

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      The loss of TDP-43 function, as often seen in neurodegenerative diseases, blocks trafficking of recycling endosomes and impairs the proper localization of cell surface receptors.

    5. PRC2 preserves intestinal progenitors and restricts secretory lineage commitment

      Fulvio Chiacchiera, Alessandra Rossi, SriGanesh Jammula, Marika Zanotti and Diego Pasini

      Version of Record online: 1 SEP 2016 | DOI: 10.15252/embj.201694550

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      PRC2 exerts a dual role in intestinal homeostasis by controlling progenitor cell proliferation via repression of Cdkn2a and restricting secretory commitment by targeting key regulators of cell differentiation.

    6. Myeloid leukemia with transdifferentiation plasticity developing from T-cell progenitors

      Pia Riemke, Melinda Czeh, Josephine Fischer, Carolin Walter, Saeed Ghani, Matthias Zepper, Konstantin Agelopoulos, Stephanie Lettermann, Marie L Gebhardt, Nancy Mah, Andre Weilemann, Michael Grau, Verena Gröning, Torsten Haferlach, Dido Lenze, Ruud Delwel, Marco Prinz, Miguel A Andrade-Navarro, Georg Lenz, Martin Dugas, Carsten Müller-Tidow and Frank Rosenbauer

      Version of Record online: 29 AUG 2016 | DOI: 10.15252/embj.201693927

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      Oncogenic transformation of mouse early lymphoid progenitors with non-committed lineage identity gives rise to myeloid leukemic cells in vivo, retaining epigenetic T-cell memory. AML conversion is promoted by Jak/Stat signaling.

    7. Aneuploid embryonic stem cells exhibit impaired differentiation and increased neoplastic potential

      Meili Zhang, Li Cheng, Yuyan Jia, Guang Liu, Cuiping Li, Shuhui Song, Allan Bradley and Yue Huang

      Version of Record online: 24 AUG 2016 | DOI: 10.15252/embj.201593103

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      Aneuploid mouse ES cell lines display impaired differentiation, but increased self-renewal and tumorigenic potential, which can be rescued by extracellular BMP4.

    8. Tryptophan-rich basic protein (WRB) mediates insertion of the tail-anchored protein otoferlin and is required for hair cell exocytosis and hearing

      Christian Vogl, Iliana Panou, Gulnara Yamanbaeva, Carolin Wichmann, Sara J Mangosing, Fabio Vilardi, Artur A Indzhykulian, Tina Pangršič, Rosamaria Santarelli, Montserrat Rodriguez-Ballesteros, Thomas Weber, Sangyong Jung, Elena Cardenas, Xudong Wu, Sonja M Wojcik, Kelvin Y Kwan, Ignacio del Castillo, Blanche Schwappach, Nicola Strenzke, David P Corey, Shuh-Yow Lin and Tobias Moser

      Version of Record online: 25 JUL 2016 | DOI: 10.15252/embj.201593565

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      ER membrane insertion of the sensory hair cell component otoferlin depends on the tail-anchored protein insertion TRC40 pathway, whose disruption impairs synaptic vesicle replenishment and hearing.


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