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  • Cezanne (OTUD7B) regulates HIF‐1α homeostasis in a proteasome‐independent manner
    1. Anja Bremm*,1,2,
    2. Sonia Moniz3,
    3. Julia Mader1,
    4. Sonia Rocha*,3 and
    5. David Komander*,2
    1. 1Buchmann Institute for Molecular Life Sciences, Institute of Biochemistry II, Goethe University, Frankfurt (Main), Germany
    2. 2Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    3. 3College of Life Sciences, Centre for Gene Regulation and Expression, University of Dundee, Dundee, UK
    1. * Corresponding author. Tel: +49 69 79842510; E‐mail: bremm{at}em.uni-frankfurt.de

      Corresponding author. Tel: +44 1382 385792; E‐mail: s.rocha{at}dundee.ac.uk

      Corresponding author. Tel: +44 1223 267160; E‐mail: dk{at}mrc-lmb.cam.ac.uk

    The Lys11 linkage‐specific deubiquitinase Cezanne is shown to regulate HIF‐1α protein stability. Intriguingly, Cezanne‐mediated stabilization depends on pVHL, but not hydroxylation, and is proteasome‐independent.

    Synopsis

    The Lys11 linkage‐specific deubiquitinase Cezanne is shown to regulate HIF‐1α protein stability. Intriguingly, Cezanne‐mediated stabilization depends on pVHL, but not hydroxylation, and is proteasome‐independent.

    • Cezanne regulates the cellular adaptation to hypoxia by preventing proteasome‐independent degradation of the transcription factor HIF‐1α.

    • Loss of Cezanne results in decreased HIF‐1α target gene expression and increased cell death in hypoxia.

    • HIF‐1α is modified with Lys11‐ and Lys48‐linked ubiquitin conjugates.

    • Cezanne may affect HIF‐1α degradation through chaperone‐mediated autophagy.

    • Cezanne
    • HIF‐1α
    • hypoxia
    • Lys11‐linked ubiquitin chains
    • ubiquitin
    • Received March 30, 2014.
    • Revision received September 24, 2014.
    • Accepted September 29, 2014.

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Anja Bremm, Sonia Moniz, Julia Mader, Sonia Rocha, David Komander
  • MicroRNA‐15b promotes neurogenesis and inhibits neural progenitor proliferation by directly repressing TET3 during early neocortical development
    1. Xiaohui Lv1,,
    2. Huihui Jiang1,,
    3. Yanli Liu1,
    4. Xuepei Lei1 and
    5. Jianwei Jiao*,1
    1. 1State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    1. *Corresponding author. Tel: +86 10 64806335; E‐mail: jwjiao{at}ioz.ac.cn
    1. These authors contributed equally to this work

    This study shows that miR‐15b targets TET3 and that miR‐15b and TET3 contribute to maintain the NPC pool during early neocortical development.

    Synopsis

    This study shows that miR‐15b targets TET3 and that miR‐15b and TET3 contribute to maintain the NPC pool during early neocortical development.

    • miR‐15b is expressed in neural progenitors, represses NPC proliferation, increases the number of basal progenitors, and promotes neurogenesis.

    • miR‐15b directly targets TET3 to epigenetically repress cyclin D1 expression and NPC proliferation.

    • miR‐15b
    • neocortical development
    • neural progenitors
    • proliferation
    • TET3
    • Received April 16, 2014.
    • Revision received September 14, 2014.
    • Accepted September 22, 2014.
    Xiaohui Lv, Huihui Jiang, Yanli Liu, Xuepei Lei, Jianwei Jiao
  • E2F1 induces miR‐224/452 expression to drive EMT through TXNIP downregulation
    1. Susanne Knoll1,
    2. Katharina Fürst1,
    3. Bhavani Kowtharapu1,
    4. Ulf Schmitz2,
    5. Stephan Marquardt1,
    6. Olaf Wolkenhauer2,
    7. Hubert Martin3 and
    8. Brigitte M Pützer*,1
    1. 1Institute of Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, Rostock, Germany
    2. 2Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany
    3. 3Department of Neuropathology, University Hospital Charité, Berlin, Germany
    1. *Corresponding author. Tel: +49 381 494 5066/68; Fax: +49 381 494 5062; E‐mail: brigitte.puetzer{at}med.uni-rostock.de

    The E2F1‐miR‐244/452‐TXNIP pathway is shown to be crucial for melanoma invasion and metastasis in vivo. By activating the expression of miR‐224/452, E2F1 leads to the downregulation of its inhibitor, TXNIP, and induces EMT.

    Synopsis

    The E2F1‐miR‐244/452‐TXNIP pathway is shown to be crucial for melanoma invasion and metastasis in vivo. By activating the expression of miR‐224/452, E2F1 leads to the downregulation of its inhibitor, TXNIP, and induces EMT.

    • In early primary tumors, high levels of TXNIP restrict E2F1 activity through p16 activation and subsequent inhibition of RB.

    • Increasingly high levels of E2F1 during cancer progression lead to the transcriptional upregulation of the miR‐224/452 cluster.

    • miR‐224 and miR‐452 repress the expression of TXNIP to induce E2F1‐dependent EMT and invasion.

    • E2F1 transcription factor
    • epithelial‐mesenchymal transition
    • melanoma metastasis
    • miRNA cluster
    • thioredoxin‐interacting protein
    • Received September 1, 2014.
    • Revision received September 18, 2014.
    • Accepted September 19, 2014.
    Susanne Knoll, Katharina Fürst, Bhavani Kowtharapu, Ulf Schmitz, Stephan Marquardt, Olaf Wolkenhauer, Hubert Martin, Brigitte M Pützer
  • Networking in academiaGenerating and enhancing relationships with your acquaintances and colleagues will create a diverse network of sponsors eager to help you succeed

    Generating and enhancing relationships with your acquaintances and colleagues will create a diverse network of sponsors eager to help you succeed

    1. Jennifer Streeter (Jennifer-streeter{at}uiowa.edu) 1
    1. 1University of Iowa, Iowa, USA

    Building a network to give you an edge is as important for scientists in academia as it is for those in industry. So how do you make it a mutually beneficial experience?

    Jennifer Streeter
  • Rules of engagementRestricting security‐sensitive research data—a European view

    Restricting security‐sensitive research data—a European view

    1. Johannes Rath (johannes.rath{at}univie.ac.at) 1
    1. 1Department of Integrative Zoology, University of Vienna, Vienna, Austria

    The recent debate about gain‐of‐function experiments with pathogens has raised the issue of how the legal system should weigh biosecurity concerns against academic freedom.

    Johannes Rath
  • Authorship inflation is unethical
    1. David Shaw (david.shaw{at}unibas.ch) 1
    1. 1Institute for Biomedical Ethics, University of Basel, Basel, Switzerland

    The response by David Shaw.

    David Shaw
  • Reawakening anaesthesia researchAnaesthesia—one of the greatest achievements of medicine—remains unexplained, but a slew of new studies may help to solve the mystery

    Anaesthesia—one of the greatest achievements of medicine—remains unexplained, but a slew of new studies may help to solve the mystery

    1. Andrea Rinaldi, Freelance science writer (rinaldi.ac{at}gmail.com) 1
    1. 1 Cagliari, Italy

    An explosion of studies on the molecular mechanism of anaesthetics and their effect on neural circuits is bringing us closer to solving the long‐standing scientific puzzle of how anaesthesia actually works.

    Andrea Rinaldi