Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation.

摘要: Summary FAK is known as an integrin- and growth factor-associated tyrosine kinase promoting cell motility. Here we show that, during mouse development, inactivation results in p53- p21-dependent mesodermal arrest. Reconstitution of primary −/− p21 fibroblasts revealed that FAK, in a kinase-independent manner, facilitates p53 turnover via enhanced Mdm2-dependent ubiquitination. by required FERM F1 lobe binding to p53, F2 lobe-mediated nuclear localization, F3 for connections Mdm2 proteasomal degradation. Staurosporine or loss adhesion FERM-dependent accumulation. In human cells, knockdown raised p53-p21 levels slowed proliferation but did not cause apoptosis. Notably, plus cisplatin triggered p53-dependent apoptosis, which was rescued either full-length re-expression. These studies define a scaffolding role facilitating survival through degradation under conditions cellular stress.