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Elife. 2019 Feb 8;8. pii: e41036. doi: 10.7554/eLife.41036.

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

Author information

1
Center for Biological Systems Analysis, University of Freiburg, Freiburg, Germany.
2
Faculty of Biology, Ludwig-Maximilians-University Munich, Munich, Germany.
3
Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany.
4
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
5
Institute for Genetics, University of Cologne, Cologne, Germany.
6
Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Freiburg, Germany.
7
Centre for Integrative Biological Signalling Studies (CIBSS), University of Freiburg, Freiburg, Germany.
8
Center for Molecular Medicine Cologne, University of Cologne, 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.

KEYWORDS:

D. melanogaster; G2 arrest; JNK; cell biology; developmental biology; injury-induced apoptosis; non-autonomous overgrowth; senescence; tissue damage

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