title: TAZ promotes PC2 degradation through a SCFbeta-Trcp E3 ligase complex.
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 beta-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 SCF(beta-Trcp) E3 ubiquitin ligase pathway. Replacements of serines in a phosphodegron motif in TAZ prevent beta-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.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tian
authors.forename: Robert
authors.initials: R
authors.lastname: Kolb
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Hong
authors.forename: John
authors.initials: J
authors.lastname: Carroll
authors.forename: Dawei
authors.initials: D
authors.lastname: Li
authors.forename: John
authors.initials: J
authors.lastname: You
authors.forename: Roderick
authors.initials: R
authors.lastname: Bronson
authors.forename: Michael B
authors.initials: MB
authors.lastname: Yaffe
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Thomas
authors.initials: T
authors.lastname: Benjamin
mesh_terms: D000217:Acyltransferases; D000818:Animals; D002460:Cell Line; D044842:Cullin Proteins / Q000378:metabolism*; D044783:F-Box Proteins / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D011233:Precipitin Tests; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism*; D050396:TRPP Cation Channels / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D000217:Acyltransferases; D044842:Cullin Proteins; D044783:F-Box Proteins; D005982:Glutathione Transferase; D011506:Proteins; D011994:Recombinant Proteins; D044843:SKP Cullin F-Box Protein Ligases; D050396:TRPP Cation Channels; D014157:Transcription Factors; D014452:Ubiquitins; C486363:tafazzin protein, mouse