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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Casein Kinase I / genetics
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Casein Kinase I / metabolism
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism
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HEK293 Cells
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Humans
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Intracellular Signaling Peptides and Proteins / chemistry
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Mice
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NIH 3T3 Cells
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Phosphorylation
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Protein Binding
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Protein Stability
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SKP Cullin F-Box Protein Ligases / genetics
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SKP Cullin F-Box Protein Ligases / metabolism*
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Signal Transduction*
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Trans-Activators
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Transcription Factors
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Transcriptional Coactivator with PDZ-Binding Motif Proteins
Substances
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Drosophila Proteins
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Intracellular Signaling Peptides and Proteins
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Trans-Activators
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Transcription Factors
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Transcriptional Coactivator with PDZ-Binding Motif Proteins
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WWTR1 protein, human
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SKP Cullin F-Box Protein Ligases
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LATS1 protein, human
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Casein Kinase I
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Protein Serine-Threonine Kinases
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hpo protein, Drosophila