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

115 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 1

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Ubiquitin-Protein Ligases
Polycystic Kidney Diseases
F-Box Proteins
Cystic Kidney Diseases
Emphysema
Zebrafish
Knockout Mice
Serine
Proteolysis
Vertebrates
Cations
Phosphorylation
polycystic kidney disease 2 protein
Calcium
Kidney
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Tian, Y., Kolb, R., Hong, J-H., Carroll, J., Li, D., You, 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

TAZ promotes PC2 degradation through a SCFβ-Trcp E3 ligase complex. / Tian, Yu; Kolb, Robert; Hong, Jeong-Ho; Carroll, John; Li, Dawei; You, John; Bronson, Roderick; Yaffe, Michael B.; Zhou, Jing; Benjamin, Thomas.

In: Molecular and Cellular Biology, Vol. 27, No. 18, 01.09.2007, p. 6383-6395.

Research output: Contribution to journalArticle

Tian, Y, Kolb, R, Hong, J-H, Carroll, J, Li, D, You, J, Bronson, R, Yaffe, MB, Zhou, J & Benjamin, T 2007, 'TAZ promotes PC2 degradation through a SCFβ-Trcp E3 ligase complex', Molecular and Cellular Biology, vol. 27, no. 18, pp. 6383-6395. https://doi.org/10.1128/MCB.00254-07
Tian, Yu ; Kolb, Robert ; Hong, Jeong-Ho ; Carroll, John ; Li, Dawei ; You, John ; Bronson, Roderick ; Yaffe, Michael B. ; Zhou, Jing ; Benjamin, Thomas. / TAZ promotes PC2 degradation through a SCFβ-Trcp E3 ligase complex. In: Molecular and Cellular Biology. 2007 ; Vol. 27, No. 18. pp. 6383-6395.
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