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Molecular and Cellular Biology, September 2007, p. 6383-6395, Vol. 27, No. 18
0270-7306/07/$08.00+0     doi:10.1128/MCB.00254-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

TAZ Promotes PC2 Degradation through a SCFß-Trcp E3 Ligase Complex{triangledown} ,{dagger}

Yu Tian,1 Robert Kolb,2 Jeong-Ho Hong,3,4 John Carroll,1 Dawei Li,1 John You,1 Roderick Bronson,1 Michael B. Yaffe,3 Jing Zhou,2 and Thomas Benjamin1*

Department of Pathology,1 Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115,2 Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139,3 School of Life Sciences and Biotechnology, Korea University, Anam-Dong, Seongbuk-Gu, Seoul 136-701, South Korea4

Received 12 February 2007/ Returned for modification 15 March 2007/ Accepted 22 June 2007

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 ß-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 SCFß-Trcp E3 ubiquitin ligase pathway. Replacements of serines in a phosphodegron motif in TAZ prevent ß-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.

* Corresponding author. Mailing address: Department of Pathology, Harvard Medical School, Boston, MA 02115. Phone: (617) 432-1959. Fax: (617) 432-2689. E-mail: thomas_benjamin{at}hms.harvard.edu

{triangledown} Published ahead of print on 16 July 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, September 2007, p. 6383-6395, Vol. 27, No. 18
0270-7306/07/$08.00+0     doi:10.1128/MCB.00254-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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