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  • Correspondence
    Response by Caplan et al
    <div xmlns="http://www.w3.org/1999/xhtml">Response by Caplan <em>et al</em></div>
    1. Arthur L Caplan (arthur.caplan{at}nyumc.org)1,
    2. Carolyn Plunkett1,2,
    3. Brendan Parent1 and
    4. Michael Shen3
    1. 1Division of Medical Ethics, New York University Langone Medical Center, New York, NY, USA
    2. 2Philosophy Department, The Graduate Center CUNY, New York, NY, USA
    3. 3Institute for Systems Genetics, New York University Langone Medical Center, New York, NY, USA

    The original authors' response.

    Arthur L Caplan, Carolyn Plunkett, Brendan Parent, Michael Shen
  • Correspondence
    Carl Woese's worries about the role of bio‐engineering
    Carl Woese's worries about the role of bio‐engineering
    1. Min‐Liang Wong (mlwong{at}dragon.nchu.edu.tw)1
    1. 1Department of Veterinary Medicine, National Chung‐Hsing University, Taichung, Taiwan

    A comment on “No time to waste—the ethical challenges created by CRISPR”.

    Min‐Liang Wong
  • Correspondence
    No time to waste on the road to a liberal eugenics?
    No time to waste on the road to a liberal eugenics?
    1. Guenther Witzany (witzany{at}sbg.at)1
    1. 1Telos‐Philosophische Praxis, Buermoos, Austria

    A comment on “No time to waste—the ethical challenges created by CRISPR”.

    Guenther Witzany
  • Article
    NAT10 regulates p53 activation through acetylating p53 at K120 and ubiquitinating Mdm2
    NAT10 regulates p53 activation through acetylating p53 at K120 and ubiquitinating Mdm2
    1. Xiaofeng Liu1,2,
    2. Yuqin Tan1,2,
    3. Chunfeng Zhang1,3,
    4. Ying Zhang1,4,
    5. Liangliang Zhang1,2,
    6. Pengwei Ren1,2,
    7. Hongkui Deng1,2,
    8. Jianyuan Luo1,3,5,
    9. Yang Ke1,4 and
    10. Xiaojuan Du*,1,2
    1. 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China
    2. 2Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
    3. 3Department of Medical Genetics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
    4. 4Laboratory of Genetics, Peking University School of Oncology, Peking University Cancer Hospital & Institute, Beijing, China
    5. 5Department of Medical & Research Technology, School of Medicine, University of Maryland, Baltimore, MD, USA
    1. *Corresponding author. Tel: +86 10 82801547; Fax: +86 10 82801130; E‐mail: duxiaojuan100{at}bjmu.edu.cn

    NAT10 acts as an E3 ligase for Mdm2 to promote Mdm2 degradation and stabilizes p53 under normal conditions. While under DNA damage conditions, NAT10 prevents Mdm2–p53 interaction by binding to p53 and acetylates p53, thus regulating p53‐mediated cell cycle arrest and apoptosis.

    Synopsis

    NAT10 acts as an E3 ligase for Mdm2 to promote Mdm2 degradation and stabilizes p53 under normal conditions. While under DNA damage conditions, NAT10 prevents Mdm2–p53 interaction by binding to p53 and acetylates p53, thus regulating p53‐mediated cell cycle arrest and apoptosis.

    • NAT10 promotes Mdm2 ubiquitination and degradation with its E3 ligase activity under normal conditions.

    • NAT10 acetylates p53 at K120.

    • NAT10 translocates to nucleoplasm to bind and acetylate p53 at K120 upon cellular stress, thus contributing to p53 activation.

    • acetylation
    • E3 ligase
    • Mdm2
    • NAT10
    • p53
    • Received April 7, 2015.
    • Revision received November 14, 2015.
    • Accepted January 11, 2016.

    This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

    Xiaofeng Liu, Yuqin Tan, Chunfeng Zhang, Ying Zhang, Liangliang Zhang, Pengwei Ren, Hongkui Deng, Jianyuan Luo, Yang Ke, Xiaojuan Du
  • Article
    Feedback regulation between atypical E2Fs and APC/CCdh1 coordinates cell cycle progression
    <div xmlns="http://www.w3.org/1999/xhtml">Feedback regulation between atypical E2Fs and APC/C<sup>C</sup><sup>dh1</sup> coordinates cell cycle progression</div>
    1. Michiel Boekhout14,
    2. Ruixue Yuan2,
    3. Annelotte P Wondergem2,
    4. Hendrika A Segeren2,
    5. Elsbeth A van Liere2,
    6. Nesibu Awol2,
    7. Imke Jansen2,
    8. Rob MF Wolthuis15,
    9. Alain de Bruin*,2,3 and
    10. Bart Westendorp*,2
    1. 1Division of Cell Biology I (B5), The Netherlands Cancer Institute (NKI‐AvL), Amsterdam, The Netherlands
    2. 2Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
    3. 3Department of Pediatrics, Division of Molecular Genetics, University Medical Center Groningen University of Groningen, Groningen, The Netherlands
    4. 4Molecular Biology Program, Memorial Sloan‐Kettering Cancer Center, New York, NY, USA
    5. 5Department of Clinical Genetics (Division of Oncogenetics), VUmc Medical Faculty, VUmc and VUmc Cancer Center Amsterdam, CCA/V‐ICI Research Program Oncogenesis, Amsterdam, The Netherlands
    1. * Corresponding author. Tel: +31 302534293; E‐mail: a.debruin{at}uu.nl
      Corresponding author. Tel: +31 302535313; E‐mail: b.westendorp{at}uu.nl

    This study shows that the APC/C targets E2F7 and E2F8 for degradation, while these atypical E2Fs in their turn activate the APC/C by repressing its main inhibitors. Disturbing this feedback alters the oscillating expression of critical S phase genes and perturbs DNA replication.

    Synopsis

    This study shows that the APC/C targets E2F7 and E2F8 for degradation, while these atypical E2Fs in their turn activate the APC/C by repressing its main inhibitors. Disturbing this feedback alters the oscillating expression of critical S phase genes and perturbs DNA replication.

    • The transcription repressors E2F7 and E2F8 are targeted for proteasomal degradation by APC/CCdh1 during mitotic exit and G1 phase.

    • Expressing KEN mutant stable versions of E2F7/8 in G1 leads to unscheduled repression of cell cycle genes, perturbed DNA replication, and cell death.

    • E2F7 and E2F8 can activate APC/CCdh1 by repressing its main inhibitors Emi1 and the cyclins A and E.

    • Interdependent activity of E2F7, E2F8, and APC/C balances expression of partially overlapping sets of key cell cycle genes.

    • anaphase‐promoting complex
    • CDH1
    • cell cycle
    • DNA replication
    • E2F
    • Received July 8, 2015.
    • Revision received January 7, 2016.
    • Accepted January 7, 2016.
    Michiel Boekhout, Ruixue Yuan, Annelotte P Wondergem, Hendrika A Segeren, Elsbeth A van Liere, Nesibu Awol, Imke Jansen, Rob MF Wolthuis, Alain de Bruin, Bart Westendorp
  • Article
    GemC1 controls multiciliogenesis in the airway epithelium
    GemC1 controls multiciliogenesis in the airway epithelium
    1. Marina Arbi1,
    2. Dafni‐Eleftheria Pefani13,
    3. Christina Kyrousi2,,
    4. Maria‐Eleni Lalioti2,
    5. Argyro Kalogeropoulou2,
    6. Anastasios D Papanastasiou14,
    7. Stavros Taraviras2 and
    8. Zoi Lygerou*,1
    1. 1Laboratory of Biology, School of Medicine, University of Patras, Patras, Greece
    2. 2Laboratory of Physiology, School of Medicine University of Patras, Patras, Greece
    3. 3Department of Oncology, CRUK/MRC Oxford Institute University of Oxford, Oxford, UK
    4. 4Department of Pathology, Patras General Hospital and Clinical and Molecular Oncology Laboratory, Division of Oncology, School of Medicine University of Patras, Patras, Greece
    1. *Corresponding author. Tel: +30 2610 997610; E‐mail: lygerou{at}med.upatras.gr
    1. These authors contributed equally to this work

    GemC1 is required for the differentiation of multiciliated airway epithelial cells. It induces McIdas and FoxJ1 expression, promoting early steps of ciliogenesis.

    Synopsis

    GemC1 is required for the differentiation of multiciliated airway epithelial cells. It induces McIdas and FoxJ1 expression, promoting early steps of ciliogenesis.

    • GemC1 is specifically expressed in ciliated epithelia, and its ectopic expression is sufficient to induce McIdas and Foxj1, the earliest known transcriptional regulators of ciliogenesis.

    • GemC1 directly transactivates the promoters of MCIDAS and FOXJ1. It co‐operates with E2F5 and is inhibited by geminin.

    • Mice deficient for GemC1 are born with airway epithelia devoid of multiciliated cells, exhibit severe postnatal growth retardation, and die soon after birth.

    • cell cycle
    • ciliary epithelia
    • ciliopathies
    • McIdas
    • respiratory disorders
    • Received June 18, 2015.
    • Revision received December 22, 2015.
    • Accepted January 4, 2016.
    Marina Arbi, Dafni‐Eleftheria Pefani, Christina Kyrousi, Maria‐Eleni Lalioti, Argyro Kalogeropoulou, Anastasios D Papanastasiou, Stavros Taraviras, Zoi Lygerou
  • Scientific Report
    Chromosome misalignments induce spindle‐positioning defects
    Chromosome misalignments induce spindle‐positioning defects
    1. Mihoko A Tame1,,
    2. Jonne A Raaijmakers1,,
    3. Pavel Afanasyev2 and
    4. René H Medema*,1
    1. 1Department of Cell Biology and Cancer Genomics Center, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    2. 2The Maastricht Multimodal Molecular Imaging Institute, Maastricht University, Maastricht, The Netherlands
    1. *Corresponding author. Tel: +31 20 5121990; Fax: +31 205122011; E‐mail: r.medema{at}nki.nl
    1. These authors contributed equally to this work

    Chromosome misalignments result in the cortical displacement of LGN, followed by defects in spindle positioning. The disruption of cortical LGN is caused by kinetochore‐associated PLK1 on the uncongressed chromosomes.

    Synopsis

    Chromosome misalignments result in the cortical displacement of LGN, followed by defects in spindle positioning. The disruption of cortical LGN is caused by kinetochore‐associated PLK1 on the uncongressed chromosomes.

    • Chromosome alignment defects entail perturbations in spindle positioning.

    • Misaligned chromosomes actively disrupt the cortical association of LGN.

    • Kinetochore‐associated PLK1 on misaligned chromosomes negatively regulates LGN localization at the cortex.

    • spindle positioning
    • chromosome misalignment
    • LGN
    • PLK1
    • micropatterning
    • Received August 6, 2015.
    • Revision received December 8, 2015.
    • Accepted January 4, 2016.
    Mihoko A Tame, Jonne A Raaijmakers, Pavel Afanasyev, René H Medema