Identification of mechanism that couples multisite phosphorylation of Yes-associated protein (YAP) with transcriptional coactivation and regulation of apoptosis.

ABSTRACT: The transcriptional coactivator Yes-associated protein (YAP) has been implicated in tumorigenesis by regulating cell proliferation and apoptosis. YAP interacts with the transcription factor TEAD and is essential in mediating TEAD-dependent gene expression. Here we show that YAP is hyperphosphorylated and activated in response to genotoxic stress such as UV irradiation and cisplatin treatment. Using high resolution mobility shift assay for phosphorylated proteins, we identified multiple sites of phosphorylation induced by UV irradiation. Pretreatment with p38 and JNK inhibitors completely suppressed the mobility retardation of phosphorylated YAP in UV-irradiated cells. Co-immunoprecipitation experiments showed that the physical interaction of YAP with TEAD was markedly enhanced by UV irradi

SUBMITTER: Lee KK 

PROVIDER: S-EPMC3308740 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature