A Functional Interaction between RIP140 and PGC-1α Regulates the Expression of the Lipid Droplet Protein CIDEA

Abstract

Nuclear receptors activate or repress target genes depending on the recruitment of coactivators or corepressors. The corepressor RIP140 and the PPAR coactivator 1α (PGC-1α) both play key roles in the regulated transcription of genes involved in energy homeostasis. We investigated the roles of RIP140 and PGC-1α in controlling the expression of CIDEA, an important regulatory factor in adipose cell function and obesity. Ectopically expressed CIDEA surrounded lipid droplets in brown adipocytes and induced the formation of lipid droplets in nonadipogenic cell lines. The expression and promoter activity of CIDEA was repressed by RIP140 and induced by PGC-1α, mediated through the binding of estrogen-related receptor α and NRF-1 to their cognate binding sites. Importantly, we demonstrate that RIP140 interacts directly with PGC-1α and suppresses its activity. The direct antagonism of PGC-1α by RIP140 provides a mechanism for regulating target gene transcription via nuclear receptor-dependent and -independent pathways.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://mcb.asm.org/ .

ACKNOWLEDGMENTS

We thank R. Scarpulla, A. Kakizuka, and B. Herzog for their gifts of plasmids, Hongwu Chen for RIP140 antibody, Greg Brook for assistance with confocal microscopy, and the members of the Molecular Endocrinology Group for help and advice.

This work was supported by Wellcome Trust program grants 061930/Z/00/Z and 079200/Z/06/Z and BBSRC grant BB/C504327/1.