PRIC295, a Nuclear Receptor Coactivator, Identified from PPAR𝛼-Interacting Cofactor Complex

Abstract

The peroxisome proliferator-activated receptor-𝛼 (PPAR𝛼) plays a key role in lipid metabolism and energy combustion. Chronic activation of PPAR𝛼 in rodents leads to the development of hepatocellular carcinomas. The ability of PPAR𝛼 to induce expression of its target genes depends on Mediator, an evolutionarily conserved complex of cofactors and, in particular, the subunit 1 (Med1) of this complex. Here, we report the identification and characterization of PPAR𝛼-interacting cofactor (PRIC)-295 (PRIC295), a novel coactivator protein, and show that it interacts with the Med1 and Med24 subunits of the Mediator complex. PRIC295 contains 10 LXXLL signature motifs that facilitate nuclear receptor binding and interacts with PPAR𝛼 and five other members of the nuclear receptor superfamily in a ligand-dependent manner. PRIC295 enhances the transactivation function of PPAR𝛼, PPAR𝛾, and ER𝛼. These data demonstrate that PRIC295 interacts with nuclear receptors such as PPAR𝛼 and functions as a transcription coactivator under in vitro conditions and may play an important role in mediating the effects in vivo as a member of the PRIC complex with Med1 and Med24.