AKT-1 regulates DNA-damage-induced germline apoptosis in C. elegans.
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.
Quevedo
Celia
C
Cancer Research Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Kaplan
David R
DR
Derry
W Brent
WB
D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000528:radiation effects; D051858:Forkhead Transcription Factors; D005854:Germ Cells / Q000166:cytology*; D009154:Mutation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D011839:Radiation, Ionizing
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D051057:Proto-Oncogene Proteins c-akt; C494915:akt-1 protein, C elegans; C494916:akt-2 protein, C elegans