PUBLICATION
TAZ promotes PC2 degradation through a SCF{beta}-Trcp E3 Ligase Complex
- Authors
- Tian, Y., Kolb, R., Hong, J.H., Carroll, J., Li, D., You, J., Bronson, R., Yaffe, M.B., Zhou, J., and Benjamin, T.
- ID
- ZDB-PUB-070726-20
- Date
- 2007
- Source
- Molecular and cellular biology 27(18): 6383-6395 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Line
- Cullin Proteins/metabolism*
- F-Box Proteins/metabolism*
- Fluorescent Antibody Technique, Indirect
- Glutathione Transferase/metabolism
- Humans
- Immunohistochemistry
- Kidney/cytology
- Mice
- Mice, Knockout
- Models, Biological
- Precipitin Tests
- Proteins/genetics
- Proteins/metabolism*
- Recombinant Proteins/metabolism
- SKP Cullin F-Box Protein Ligases/genetics
- SKP Cullin F-Box Protein Ligases/metabolism*
- TRPP Cation Channels/metabolism*
- Transcription Factors/genetics
- Transcription Factors/metabolism*
- Ubiquitins/metabolism
- PubMed
- 17636028 Full text @ Mol. Cell. Biol.
Citation
Tian, Y., Kolb, R., Hong, J.H., Carroll, J., Li, D., You, J., Bronson, R., Yaffe, M.B., Zhou, J., and Benjamin, T. (2007) TAZ promotes PC2 degradation through a SCF{beta}-Trcp E3 Ligase Complex. Molecular and cellular biology. 27(18):6383-6395.
Abstract
Studies of a TAZ knockout mouse reveal a novel function of the transcriptional regulator TAZ, viz., 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. Co-expression of a cytoplasmic fragment of polycystin-1 blocks 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping