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 journalArticle

120 Citations (Scopus)

Abstract

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
Volume27
Issue number18
DOIs
Publication statusPublished - 2007 Sep

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Tian, Y., Kolb, R., Hong, J. H., Carroll, J., Li, D., You, J., Bronson, R., Yaffe, M. B., Zhou, J., & Benjamin, T. (2007). TAZ promotes PC2 degradation through a SCFβ-Trcp E3 ligase complex. Molecular and cellular biology, 27(18), 6383-6395. https://doi.org/10.1128/MCB.00254-07