1. JNK-dependent cell cycle stalling in G2 promotes survival and senescence-like phenotypes in tissue stress
- Author
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Anne-Kathrin Classen, Janhvi Jaiswal, Mirka Uhlirova, Isabelle Grass, Gábor Csordás, and Andrea Cosolo
- Subjects
0301 basic medicine ,senescence ,Cell cycle checkpoint ,Carcinogenesis ,Apoptosis ,0302 clinical medicine ,non-autonomous overgrowth ,Biology (General) ,Cellular Senescence ,D. melanogaster ,G2 arrest ,biology ,General Neuroscience ,tissue damage ,General Medicine ,Cell cycle ,Cell biology ,G2 Phase Cell Cycle Checkpoints ,Drosophila melanogaster ,Imaginal Discs ,Medicine ,Cell Division ,Research Article ,MAP Kinase Signaling System ,QH301-705.5 ,Cdc25 ,Science ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Paracrine signalling ,Downregulation and upregulation ,Stress, Physiological ,Animals ,Humans ,Cell Proliferation ,Wound Healing ,General Immunology and Microbiology ,JNK Mitogen-Activated Protein Kinases ,Cell Cycle Checkpoints ,Cell Biology ,030104 developmental biology ,biology.protein ,Ectopic expression ,JNK ,injury-induced apoptosis ,Wound healing ,030217 neurology & neurosurgery ,Developmental Biology - 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.
- Published
- 2019