An adipogenic cofactor bound by the differentiation domain of PPARgamma

EMBO J. 1999 Jul 1;18(13):3676-87. doi: 10.1093/emboj/18.13.3676.

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 types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipocytes / cytology*
  • Adipocytes / metabolism
  • 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 / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / chemistry*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Substrate Specificity
  • Trans-Activators
  • Transcription Factors / agonists
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic / genetics
  • Transfection
  • Yeasts / genetics

Substances

  • Azo Compounds
  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Estrogen
  • Recombinant Fusion Proteins
  • Scand1 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • oil red O

Associated data

  • GENBANK/AF220501