JNK-dependent cell cycle stalling in G2 promotes survival and senescence-like phenotypes in tissue stress.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30735120.
- Also identified by DOI 10.7554/eLife.41036 and PMC identifier 6389326.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The restoration of homeostasis after tissue damage relies on proper spatial-temporal control of damage-induced apoptosis and compensatory proliferation. In <i>Drosophila</i> 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 <i>stg</i> 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.
Medical subject headings
- Cellular Senescence
- Imaginal Discs
- JNK Mitogen-Activated Protein Kinases
- Stress, Physiological