p53 Regulation of G2 Checkpoint Is Retinoblastoma Protein Dependent
AUTOR(ES)
Flatt, Patricia M.
FONTE
American Society for Microbiology
RESUMO
In the present study, we investigated the role of p53 in G2 checkpoint function by determining the mechanism by which p53 prevents premature exit from G2 arrest after genotoxic stress. Using three cell model systems, each isogenic, we showed that either ectopic or endogenous p53 sustained a G2 arrest activated by ionizing radiation or adriamycin. The mechanism was p21 and retinoblastoma protein (pRB) dependent and involved an initial inhibition of cyclin B1-Cdc2 activity and a secondary decrease in cyclin B1 and Cdc2 levels. Abrogation of p21 or pRB function in cells containing wild-type p53 blocked the down-regulation of cyclin B1 and Cdc2 expression and led to an accelerated exit from G2 after genotoxic stress. Thus, similar to what occurs in p21 and p53 deficiency, pRB loss can uncouple S phase and mitosis after genotoxic stress in tumor cells. These results indicate that similar molecular mechanisms are required for p53 regulation of G1 and G2 checkpoints.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85790Documentos Relacionados
- p53 regulates a G2 checkpoint through cyclin B1
- Wip1 confers G2 checkpoint recovery competence by counteracting p53-dependent transcriptional repression
- Mechanisms of G2 Arrest in Response to Overexpression of p53
- Hypoxia induces accumulation of p53 protein, but activation of a G1-phase checkpoint by low-oxygen conditions is independent of p53 status.
- Accumulation of wild-type p53 protein upon gamma-irradiation induces a G2 arrest-dependent immunoglobulin kappa light chain gene expression.
