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- Title
An adipogenic cofactor bound by the differentiation domain of PPARgamma.
- Authors
Castillo, G; Brun, R P; Rosenfield, J K; Hauser, S; Park, C W; Troy, A E; Wright, M E; Spiegelman, B M
- Abstract
Ligand activation of the nuclear receptor PPARgamma induces adipogenesis and increases insulin sensitivity, while activation of other PPAR isoforms (-alpha and -delta) induces little or no fat cell differentiation. Expression and activation of chimeras formed between PPARgamma and PPARdelta in fibroblasts has allowed us to localize a major domain of PPARgamma responsible for adipogenesis to the N-terminal 138 amino acids, a region with AF-1 transcriptional activity. Using this region of PPARgamma as bait, we have used a yeast two-hybrid screen to clone a novel protein, termed PGC-2, containing a partial SCAN domain. PGC-2 binds to and increases the transcriptional activity of PPARgamma but does not interact with other PPARs or most other nuclear receptors. Ectopic expression of PGC-2 in preadipocytes containing endogenous PPARgamma causes a dramatic increase in fat cell differentiation at both the morphological and molecular levels. These results suggest that interactions between PGC-2, a receptor isoform-selective cofactor and PPARgamma contribute to the adipogenic action of this receptor.
- Publication
The EMBO journal, 1999, Vol 18, Issue 13, p3676
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1093/emboj/18.13.3676