An adipogenic cofactor bound by the differentiation domain of PPARgamma.
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.
Pubmed ID: 10393183 RIS Download
Adipocytes | Amino Acid Sequence | Animals | Azo Compounds | Base Sequence | Cell Differentiation | Cell Line | Cloning, Molecular | Gene Expression Regulation | Mice | Molecular Sequence Data | Protein Binding | Protein Isoforms | RNA, Messenger | Receptors, Cytoplasmic and Nuclear | Receptors, Estrogen | Recombinant Fusion Proteins | Stem Cells | Substrate Specificity | Transcription Factors | Transcription, Genetic | Transfection | Yeasts