Receptor-interacting protein 140 interacts with and inhibits transactivation by, peroxisome proliferator-activated receptor α and liver-X-receptor α Journal Articles uri icon

  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All


  • Receptor interacting protein 140 (RIP140), a previously identified putative ligand-dependent coactivator of nuclear hormone receptors, was isolated by yeast two-hybrid cloning as a factor that interacts with peroxisome proliferator-activated receptor alpha (PPARalpha). This interaction in yeast required the integrity of the carboxyl-terminal, ligand-dependent activation domain of PPARalpha. However, protein binding studies carried out in vitro showed that full-length RIP140 bound efficiently to PPARalpha in the absence of exogenously added ligand. RIP140 also bound strongly to the liver-X-receptor (LXRalpha) in the absence of an activator for this receptor. In contrast, a strong interaction of RIP140 with the PPARalpha and LXRalpha heterodimerization partner retinoid-X-receptor alpha (RXRalpha) required the presence of its cognate ligand, 9-cis retinoic acid. Transfection analysis in mammalian cells demonstrated that RIP140 antagonized PPARalpha/RXRalpha- and LXRalpha/RXRalpha-mediated signaling. Our findings identify RIP140 as a novel modulator of transcriptional activation mediated by PPARalpha and LXRalpha and indicate that RIP140 can also bind to nuclear hormone receptors in a ligand-independent manner and repress their activity.


  • Capone, John
  • S. Miyata, Kenji
  • E. McCaw, Shannon
  • M. Meertens, Lisa
  • V. Patel, Hansa
  • A. Rachubinski, Richard
  • P. Capone, John

publication date

  • November 1998

has subject area