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The N-Terminal Phosphodegron Targets Taz/Wwtr1 Protein For ScfΒ-Trcp-Dependent Degradation In Response To Phosphatidylinositol 3-Kinase Inhibition.

J Biol Chem.. 2012-07;  287(31):26245 - 26253
Wei Huang, Xianbo Lv, Chenying Liu, Zhengyu Zha, Heng Zhang, Ying Jiang, Yue Xiong, Qun-Ying Lei, and Kun-Liang Guan. Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
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摘要

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 stud... More

关键词

EMT; Glycogen Synthase Kinase 3; Phosphorylation; PI 3-Kinase (PI3K); Protein Degradation; PTEN; Hippo Pathway; TAZ