The N-terminal phosphodegron targets TAZ/WWTR1 protein for SCFβ-TrCP-dependent degradation in response to phosphatidylinositol 3-kinase inhibition.

ABSTRACT: The Hippo tumor suppressor pathway plays a major role in development and organ size control, and its dysregulation contributes to tumorigenesis. TAZ (transcriptional co-activator with PDZ-binding motif; also known as WWTR1) is a transcription co-activator acting downstream of the Hippo pathway, and increased TAZ protein levels have been associated with human cancers, such as breast cancer. Previous studies have shown that TAZ is inhibited by large tumor suppressor (LATS)-dependent phosphorylation, leading to cytoplasmic retention and ubiquitin-dependent degradation. The LATS kinase, a core component of the Hippo pathway, phosphorylates the C-terminal phosphodegron in TAZ to promote its degradation. In this study, we have found that the N-terminal phosphodegron of TAZ also plays a role in T

SUBMITTER: Huang W 

PROVIDER: S-EPMC3406709 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature