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JNK-dependent cell cycle stalling in G2 promotes survival and senescence-like phenotypes in tissue stress

  1. Andrea Cosolo
  2. Janhvi Jaiswal
  3. Gábor Csordás
  4. Isabelle Grass
  5. Mirka Uhlirova
  6. Anne-Kathrin Classen  Is a corresponding author
  1. Albert Ludwigs University Freiburg, Germany
  2. University of Cologne, Germany
Research Article
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Cite this article as: eLife 2019;8:e41036 doi: 10.7554/eLife.41036

Abstract

The restoration of homeostasis after tissue damage relies on proper spatial-temporal control of damage-induced apoptosis and compensatory proliferation. In Drosophila imaginal discs these processes are coordinated by the stress response pathway JNK. We demonstrate that JNK signaling induces a dose-dependent extension of G2 in tissue damage and tumors, resulting in either transient stalling or a prolonged but reversible cell cycle arrest. G2-stalling is mediated by downregulation of the G2/M-specific phosphatase String(Stg)/Cdc25. Ectopic expression of stg is sufficient to suppress G2-stalling and reveals roles for stalling in survival, proliferation and paracrine signaling. G2-stalling protects cells from JNK-induced apoptosis, but under chronic conditions, reduces proliferative potential of JNK-signaling cells while promoting non-autonomous proliferation. Thus, transient cell cycle stalling in G2 has key roles in wound healing but becomes detrimental upon chronic JNK overstimulation, with important implications for chronic wound healing pathologies or tumorigenic transformation.

Article and author information

Author details

  1. Andrea Cosolo

    Center for Biological Systems Analysis, Albert Ludwigs University Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3417-0713
  2. Janhvi Jaiswal

    Center for Biological Systems Analysis, Albert Ludwigs University Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Gábor Csordás

    Institute for Genetics, University of Cologne, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Isabelle Grass

    Center for Biological Systems Analysis, Albert Ludwigs University Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Mirka Uhlirova

    Institute for Genetics, University of Cologne, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5735-8287
  6. Anne-Kathrin Classen

    Center for Biological Systems Analysis, Albert Ludwigs University Freiburg, Freiburg, Germany
    For correspondence
    anne.classen@zbsa.uni-freiburg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5157-0749

Funding

Deutsche Forschungsgemeinschaft (CL490-1/1)

  • Anne-Kathrin Classen

Boehringer Ingelheim Stiftung (Plus3 Programme)

  • Anne-Kathrin Classen

Deutsche Forschungsgemeinschaft (EXC-2189 - Project ID 390939984)

  • Anne-Kathrin Classen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Andrea Musacchio, Max Planck Institute of Molecular Physiology, Germany

Publication history

  1. Received: August 15, 2018
  2. Accepted: February 6, 2019
  3. Accepted Manuscript published: February 8, 2019 (version 1)

Copyright

© 2019, Cosolo et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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