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An adipogenic cofactor bound by the differentiation domain of PPARγ
Author(s) -
Castillo Gonzalo,
Brun Regina P.,
Rosenfield Jennifer K.,
Hauser Stefanie,
Park Cheol Won,
Troy Amy E.,
Wright Margaret E.,
Spiegelman Bruce M.
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.13.3676
Subject(s) - biology , adipogenesis , cofactor , domain (mathematical analysis) , microbiology and biotechnology , computational biology , biochemistry , in vitro , enzyme , mathematical analysis , mathematics
Ligand activation of the nuclear receptor PPARγ induces adipogenesis and increases insulin sensitivity, while activation of other PPAR isoforms (‐α and ‐δ) induces little or no fat cell differentiation. Expression and activation of chimeras formed between PPARγ and PPARδ in fibroblasts has allowed us to localize a major domain of PPARγ responsible for adipogenesis to the N‐terminal 138 amino acids, a region with AF‐1 transcriptional activity. Using this region of PPARγ 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 PPARγ but does not interact with other PPARs or most other nuclear receptors. Ectopic expression of PGC‐2 in preadipocytes containing endogenous PPARγ 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 PPARγ contribute to the adipogenic action of this receptor.