p300 Functions as a Coactivator for the Peroxisome Proliferator-activated Receptor α

Abstract

The integrator protein, p300, was demonstrated to interact with mouse peroxisome proliferator-activated receptor ␣ in a ligand-enhanced manner. The PPAR␣-interacting domain of p300 was mapped to amino acids 39 -117 which interacted strongly with PPAR␣ but did not interact with retinoic acid receptor-␥ or retinoid X receptor-␣. Amino acids within the carboxyl terminus of PPAR␣ as well as residues within the hinge region were required for ligand-dependent interaction with p300. p300 enhanced the transcriptional activation properties of PPAR␣ and, therefore, can be considered a bona fide coactivator for this nuclear receptor. These observations extend the group of p300-interacting proteins to include mPPAR␣ and further characterize the molecular mechanisms of PPAR␣-mediated transcriptional regulation.

Novel Peroxisome Proliferator-activated Receptor (PPAR) γ and PPARδ Ligands Produce Distinct Biological Effects

“…Furthermore, this ligand-dependent co-activator association suggests that the novel ligands are agonists for either PPAR␥ or PPAR␦. It is worth noting that Dowell et al (33) reported recently that p300 (a homologue of CBP) can function as a co-activator for PPAR␣.…”

Convergence of Peroxisome Proliferator-activated Receptor γ and Foxo1 Signaling Pathways

“…GST pull-down assays were as described (38). The GST-Foxo1 fusion protein encoded amino acids 436 -652 of Foxo1 (the Foxo1 region identical to that identified during the twohybrid screen).…”

A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways inC. elegans

“…HNF4␣ and PPAR␣ engage a multitude of transcriptional coregulators, including the corepressor NCor (Dowell et al 1999), and coactivators such as p300/CBP (Dowell et al 1997), the PPAR␥-coactivators PGC-1␣ and PGC-1␤ (Vega et al 2000), and the Mediator subunit MED1/TRAP220/DRIP205/PBP/CRSP200 (subsequently named MED1) Malik et al 2004). In addition, med1 −/− mouse embryonic fibroblasts fail to properly express many PPAR␥ target genes, and are incapable of undergoing proper adipocyte differentiation, a PPAR␥-dependent cell fate decision (Ge et al 2002).…”