PKB/AKT phosphorylation of the transcription factor Twist-1 at Ser42 inhibits p53 activity in response to DNA damage.

摘要: Protein kinase B (PKB/Akt) is ubiquitously expressed in cells. Phosphorylation of its multiple targets response to various stimuli, including growth factors or cytokines, promotes cell survival and inhibits apoptosis. PKB upregulated many different cancers a significant amount the enzyme present activated form. Here we show that phosphorylates one anti-apoptotic proteins--transcription factor Twist-1 at Ser42. Cells expressing displayed inefficient p53 upregulation DNA damage induced by gamma-irradiation genotoxic drug adriamycin. This influenced activation target genes such as p21(Waf1) Bax led aberrant cell-cycle regulation inhibition The impaired induction these effector molecules likely be mediated PKB-dependent phosphorylation because, unlike wild-type mutant, S42A mutant did not confer resistance damage. Moreover, Ser42 was shown vivo human cancer tissues, suggesting this post-translational modification ensures functional after promotion during carcinogenesis.