Universität zu Köln

Cosolo, Andrea ORCID: 0000-0003-3417-0713, Jaiswal, Janhvi, Csordas, Gabor ORCID: 0000-0001-6871-6839, Grass, Isabelle, Uhlirova, Mirka ORCID: 0000-0002-5735-8287 and Classen, Anne-Kathrin ORCID: 0000-0001-5157-0749 (2019). JNK-dependent cell cycle stalling in G2 promotes survival and senescence-like phenotypes in tissue stress. eLife, 8. CAMBRIDGE: ELIFE SCIENCES PUBLICATIONS LTD. ISSN 2050-084X

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Cosolo, Andrea UNSPECIFIED orcid.org/0000-0003-3417-0713 UNSPECIFIED Jaiswal, Janhvi UNSPECIFIED UNSPECIFIED UNSPECIFIED Csordas, Gabor UNSPECIFIED orcid.org/0000-0001-6871-6839 UNSPECIFIED Grass, Isabelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Uhlirova, Mirka UNSPECIFIED orcid.org/0000-0002-5735-8287 UNSPECIFIED Classen, Anne-Kathrin UNSPECIFIED orcid.org/0000-0001-5157-0749 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-156776
DOI:	10.7554/eLife.41036
Journal or Publication Title:	eLife
Volume:	8
Date:	2019
Publisher:	ELIFE SCIENCES PUBLICATIONS LTD
Place of Publication:	CAMBRIDGE
ISSN:	2050-084X
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DROSOPHILA IMAGINAL DISCS; DNA-DAMAGE; SIGNALING PATHWAY; COMPENSATORY PROLIFERATION; MOLECULAR-MECHANISMS; VERSATILE TOOL; APOPTOSIS; GROWTH; REGENERATION; DEATH Multiple languages Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15677