H2O2Induces a Transient Multi-phase Cell Cycle Arrest in Mouse Fibroblasts through Modulating Cyclin D and p21Cip1Expression

摘要: To defend against the potential damages induced by reactive oxygen species, proliferating cells enter a transient cell cycle arrest. We treated mouse fibroblasts with H(2)O(2) and found that sublethal doses of multi-phase arrest at G(1), S, G(2) phases but not M phase. Western blot analysis demonstrated this is associated down-regulation cyclins D1 D3 up-regulation CKI p21(Cip1) expression. also demonstrate induction in expression least partially mediated transcriptional level can occur absence p53 function. Further immunoprecipitation kinase immunodepletion assays indicated response to treatment, cyclin Ds are repression D-CDK4, whereas accumulation responsible for inhibition E A-CDK2 activity B-CDC2 activity. These data could account following stimulation. Deletion p21(Cip1), restoration D expression, or overexpression alone insufficient effectively overcome caused H(2)O(2). By contrast, human Herpesvirus 8 K cyclin, which mimic function E, enough override On basis our findings, we propose model moderate levels induce through