Cloning and identification of mouse steroid receptor coactivator-1 (mSRC-1), as a coactivator of peroxisome proliferator-activated receptor gamma.

Yijun Zhu*, Chao Qi, C. Calandra, Sambasiva Rao Musunuri, Janardan K Reddy

*Corresponding author for this work

Research output: Contribution to journalArticle

176 Scopus citations

Abstract

Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, is expressed predominantly in adipose tissue. Forced expression of the two isoforms of this receptor, PPARgamma1 and PPARgamma2, in fibroblasts initiates a transcriptional cascade that leads to the development of adipocyte phenotype. Using the yeast two-hybrid system and GAL4-PPARgamma as bait to screen mouse liver cDNA library, we isolated a mouse steroid receptor coactivator (mSRC-1) involved in nuclear hormone receptor transcriptional activity as a mPPARgamma interactive protein. mSRC-1 cDNA we isolated contains an open reading frame of 1447 amino acids and encodes a new member of the basic helix-loop-helix-PAS domain family. We show that the binding of mSRC-1 to mPPARgamma is ligand independent and coexpression of mSRC-1 with mPPARgamma increases the transcriptional activity of mPPARgamma in the presence of mPPARgamma ligand. We have identified the presence of two putative mPPARgamma binding sites in the mSRC-1, one between residues 620 and 789, and the second between residues 1231 and 1447. These two regions exhibit different degrees of binding affinity for mPPARgamma. We also show that mSRC-1 exhibits its own constitutive transcriptional activity in the yeast as well as in mammalian cells. These results suggest that mSRC-1 interacts with PPARgamma and plays a role in the PPARgamma-mediated signaling pathway.

Original languageEnglish (US)
Pages (from-to)185-195
Number of pages11
JournalGene expression
Volume6
Issue number3
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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