TAZ promotes PC2 degradation through a SCFβ-Trcp E3 ligase complex

Yu Tian, Robert Kolb, Jeong Ho Hong, John Carroll, Dawei Li, John You, Roderick Bronson, Michael B. Yaffe, Jing Zhou, Thomas Benjamin

Research output: Contribution to journalArticlepeer-review

150 Scopus citations


Studies of a TAZ knockout mouse reveal a novel function of the transcriptional regulator TAZ, that is, as a binding partner of the F-box protein β-Trcp. TAZ-/- mice develop polycystic kidney disease (PKD) and emphysema. The calcium-permeable cation channel protein polycystin 2 (PC2) is overexpressed in kidneys of TAZ-/- mice as a result of decreased degradation via an SCFβ-Trcp E3 ubiquitin ligase pathway. Replacements of serines in a phosphodegron motif in TAZ prevent β-Trcp binding and PC2 degradation. Coexpression of a cytoplasmic fragment of polycystin 1 blocks the PC2-TAZ interaction and prevents TAZ-mediated degradation of PC2. Depletion of TAZ in zebrafish also results in a cystic kidney accompanied by overexpression of PC2. These results establish a common role of TAZ across vertebrate species in a protein degradation pathway regulated by phosphorylation and implicate deficiencies in this pathway in the development of PKD.

Original languageEnglish
Pages (from-to)6383-6395
Number of pages13
JournalMolecular and Cellular Biology
Issue number18
StatePublished - Sep 2007
Externally publishedYes


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