| AKT-1 regulates DNA-damage-induced germline apoptosis in C. elegans. | |
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MedLine Citation:
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PMID: 17276923 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The cellular response to genotoxic stress involves the integration of multiple prosurvival and proapoptotic signals that dictate whether a cell lives or dies. In mammals, AKT/PKB regulates cell survival by modulating the activity of several apoptotic proteins, including p53. In Caenorhabditis elegans, akt-1 and akt-2 regulate development in response to environmental cues by controlling the FOXO transcription factor daf-16, but the role of these genes in regulating p53-dependent apoptosis is not known. In this study, we show that akt-1 and akt-2 negatively regulate DNA-damage-induced apoptosis in the C. elegans germline. The antiapoptotic activity of akt-1 is independent of its target gene daf-16 but dependent on cep-1/p53. Although only akt-1 regulates the apoptotic activity of cep-1, both akt-1 and akt-2 modulate the intensity of the apoptotic response independently of the transcriptional activity of CEP-1. Finally, we show that AKT-1 regulates apoptosis but not cell-cycle progression downstream of the HUS-1/MRT-2 branch of the DNA damage checkpoint. |
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Authors:
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Celia Quevedo; David R Kaplan; W Brent Derry |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Current biology : CB Volume: 17 ISSN: 0960-9822 ISO Abbreviation: Curr. Biol. Publication Date: 2007 Feb |
Date Detail:
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Created Date: 2007-02-05 Completed Date: 2007-06-04 Revised Date: 2012-06-22 |
Medline Journal Info:
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Nlm Unique ID: 9107782 Medline TA: Curr Biol Country: England |
Other Details:
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Languages: eng Pagination: 286-92 Citation Subset: IM |
Affiliation:
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Cancer Research Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis* Caenorhabditis elegans / cytology, genetics, metabolism* Caenorhabditis elegans Proteins / genetics, metabolism* DNA Damage* / radiation effects Forkhead Transcription Factors Germ Cells / cytology* Mutation Proto-Oncogene Proteins c-akt / genetics, metabolism* Radiation, Ionizing |
| Chemical | |
Reg. No./Substance:
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0/Caenorhabditis elegans Proteins; 0/Forkhead Transcription Factors; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/akt-1 protein, C elegans; EC 2.7.11.1/akt-2 protein, C elegans |
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