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PMID:17276923

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Citation

Quevedo, C, Kaplan, DR and Derry, WB (2007) AKT-1 regulates DNA-damage-induced germline apoptosis in C. elegans. Curr. Biol. 17:286-92

Abstract

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.

Links

PubMed Online version:10.1016/j.cub.2006.12.038

Keywords

Animals; Apoptosis; Caenorhabditis elegans/cytology; Caenorhabditis elegans/genetics; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; DNA Damage/radiation effects; Forkhead Transcription Factors; Germ Cells/cytology; Mutation; Proto-Oncogene Proteins c-akt/genetics; Proto-Oncogene Proteins c-akt/metabolism; Radiation, Ionizing

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:AKT1

GO:0042771: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

ECO:0000315:

P

Figure 1 & 3.

complete
CACAO 6797

CAEEL:AKT1

involved_in

GO:0042771: intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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