1. An adipogenic cofactor bound by the differentiation domain of PPARgamma
- Author
-
Amy E Troy, Gonzalo Castillo, Regina P. Brun, Margaret E. Wright, Stefanie Hauser, Jennifer K. Rosenfield, Cheol Won Park, and Bruce M. Spiegelman
- Subjects
Transcription, Genetic ,Recombinant Fusion Proteins ,Cellular differentiation ,Molecular Sequence Data ,Receptors, Cytoplasmic and Nuclear ,Peroxisome proliferator-activated receptor ,Biology ,Transfection ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Substrate Specificity ,Mice ,Yeasts ,Coactivator ,Adipocytes ,Animals ,Protein Isoforms ,Amino Acid Sequence ,RNA, Messenger ,Cloning, Molecular ,Receptor ,Molecular Biology ,Transcription factor ,chemistry.chemical_classification ,Base Sequence ,General Immunology and Microbiology ,Stem Cells ,General Neuroscience ,Cell Differentiation ,Fat cell differentiation ,Cell biology ,Gene Expression Regulation ,Receptors, Estrogen ,Nuclear receptor ,chemistry ,Biochemistry ,Adipogenesis ,Trans-Activators ,Azo Compounds ,Research Article ,Protein Binding ,Transcription Factors - 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.
- Published
- 1999