JNK-dependent cell cycle stalling in G2 promotes survival and senescence-like phenotypes in tissue stress
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-d...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/41036 |
| _version_ | 1811202792679800832 |
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| author | Andrea Cosolo Janhvi Jaiswal Gábor Csordás Isabelle Grass Mirka Uhlirova Anne-Kathrin Classen |
| author_facet | Andrea Cosolo Janhvi Jaiswal Gábor Csordás Isabelle Grass Mirka Uhlirova Anne-Kathrin Classen |
| author_sort | Andrea Cosolo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:44:39Z |
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| id | doaj.art-c729baca0cf24f6fb98cdc297a44aa18 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:44:39Z |
| publishDate | 2019-02-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj.art-c729baca0cf24f6fb98cdc297a44aa182022-12-22T03:51:14ZengeLife Sciences Publications LtdeLife2050-084X2019-02-01810.7554/eLife.41036JNK-dependent cell cycle stalling in G2 promotes survival and senescence-like phenotypes in tissue stressAndrea Cosolo0https://orcid.org/0000-0003-3417-0713Janhvi Jaiswal1Gábor Csordás2https://orcid.org/0000-0001-6871-6839Isabelle Grass3Mirka Uhlirova4https://orcid.org/0000-0002-5735-8287Anne-Kathrin Classen5https://orcid.org/0000-0001-5157-0749Center for Biological Systems Analysis, University of Freiburg, Freiburg, Germany; Faculty of Biology, Ludwig-Maximilians-University Munich, Munich, GermanySpemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, GermanyCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany; Institute for Genetics, University of Cologne, Cologne, GermanyFaculty of Biology, Ludwig-Maximilians-University Munich, Munich, Germany; Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Freiburg, Germany; Centre for Integrative Biological Signalling Studies (CIBSS), University of Freiburg, Freiburg, GermanyCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany; Institute for Genetics, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, GermanyFaculty of Biology, Ludwig-Maximilians-University Munich, Munich, Germany; Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Freiburg, Germany; Centre for Integrative Biological Signalling Studies (CIBSS), University of Freiburg, Freiburg, GermanyThe 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.https://elifesciences.org/articles/41036G2 arrestJNKsenescencetissue damagenon-autonomous overgrowthinjury-induced apoptosis |
| spellingShingle | Andrea Cosolo Janhvi Jaiswal Gábor Csordás Isabelle Grass Mirka Uhlirova Anne-Kathrin Classen JNK-dependent cell cycle stalling in G2 promotes survival and senescence-like phenotypes in tissue stress eLife G2 arrest JNK senescence tissue damage non-autonomous overgrowth injury-induced apoptosis |
| title | JNK-dependent cell cycle stalling in G2 promotes survival and senescence-like phenotypes in tissue stress |
| title_full | JNK-dependent cell cycle stalling in G2 promotes survival and senescence-like phenotypes in tissue stress |
| title_fullStr | JNK-dependent cell cycle stalling in G2 promotes survival and senescence-like phenotypes in tissue stress |
| title_full_unstemmed | JNK-dependent cell cycle stalling in G2 promotes survival and senescence-like phenotypes in tissue stress |
| title_short | JNK-dependent cell cycle stalling in G2 promotes survival and senescence-like phenotypes in tissue stress |
| title_sort | jnk dependent cell cycle stalling in g2 promotes survival and senescence like phenotypes in tissue stress |
| topic | G2 arrest JNK senescence tissue damage non-autonomous overgrowth injury-induced apoptosis |
| url | https://elifesciences.org/articles/41036 |
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