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

The peroxisome proliferator-activated receptor-alpha (PPAR alpha) plays a key role in lipid metabolism and energy combustion. Chronic activation of PPARa in rodents leads to the development of hepatocellular carcinomas. The ability of PPAR alpha 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 PPAR alpha-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 PPAR alpha and five other members of the nuclear receptor superfamily in a ligand-dependent-manner. PRIC295 enhances the transactivation function of PPAR alpha, PPAR gamma, and ER alpha. These data demonstrate that PRIC295 interacts with nuclear receptors such as PPAR alpha 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.