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J Biol Chem. 2010 Nov 26;285(48):37159-69. doi: 10.1074/jbc.M110.152942. Epub 2010 Sep 21.

The hippo tumor pathway promotes TAZ degradation by phosphorylating a phosphodegron and recruiting the SCF{beta}-TrCP E3 ligase.

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1
Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology School of Medicine.

Abstract

The TAZ transcription co-activator promotes cell proliferation and epithelial-mesenchymal transition. TAZ is inhibited by the Hippo tumor suppressor pathway, which promotes TAZ cytoplasmic localization by phosphorylation. We report here that TAZ protein stability is controlled by a phosphodegron recognized by the F-box protein β-TrCP and ubiquitylated by the SCF/CRL1(β-TrCP) E3 ligase. The interaction between TAZ and β-TrCP is regulated by the Hippo pathway. Phosphorylation of a phosphodegron in TAZ by LATS primes it for further phosphorylation by CK1ε and subsequent binding by β-TrCP. Therefore, the Hippo pathway negatively regulates TAZ function by both limiting its nuclear accumulation and promoting its degradation. The phosphodegron-mediated TAZ degradation plays an important role in negatively regulating TAZ biological functions.

PMID:
20858893
PMCID:
PMC2988322
DOI:
10.1074/jbc.M110.152942
[Indexed for MEDLINE]
Free PMC Article
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