JNK-dependent cell cycle stalling in G2 promotes survival and senescence-like phenotypes in tissue stress
- Albert Ludwigs University Freiburg, Germany
- University of Cologne, Germany
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Anne-Kathrin Classen
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
- Andrea Musacchio, Max Planck Institute of Molecular Physiology, Germany
Version history
- Received: August 15, 2018
- Accepted: February 6, 2019
- Accepted Manuscript published: February 8, 2019 (version 1)
- Version of Record published: February 25, 2019 (version 2)
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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JNK-dependent cell cycle stalling in G2 promotes survival and senescence-like phenotypes in tissue stress
eLife 8:e41036.
https://doi.org/10.7554/eLife.41036
