p53 Retards cell-growth and suppresses etoposide-induced apoptosis in Pin1-deficient mouse embryonic fibroblasts

We studied the effects of Pin1, a regulatory molecule of the oncosuppressor p53, on both cell cycle arrest and apoptosis by treating primary mouse embryonic fibroblasts (MEFs) with etoposide. Etoposide induced G1 arrest in both wild-type and Pin1 null (pin1−/−) MEFs, and G2/M arrest and apoptotic cell death in MEFs lacking either p53 only (p53−/−) or both Pin1 and p53 (pin1−/−p53−/−). Both pin1−/− and pin1−/−p53−/− MEFs were enhanced the release of cytochrome c from the mitochondria, which might induce apoptosis. In response to etoposide treatment, apoptotic cell death was displayed in pin1−/−p53−/− MEFs but not in pin1−/− MEFs. These results suggest that p53 retards growth and suppresses etoposide-induced apoptosis in pin1−/− MEFs.

► Effect of Pin1 on apoptosis was studied by using pin1−/−p53−/− mouse cell. ► Pin1 inactivation facilitated apoptotic cell death in response to etoposide. ► An etoposide-induced apoptotic pathway was suppressed by p53 expression. ► Pin1 and/or p53 controls apoptosis at the post-mitochondrial level.