A functional interaction between RIP140 and PGC-1alpha regulates the expression of the lipid droplet protein CIDEA.
Nuclear receptors activate or repress target genes depending on the recruitment of coactivators or corepressors. The corepressor RIP140 and the PPAR coactivator 1alpha (PGC-1alpha) both play key roles in the regulated transcription of genes involved in energy homeostasis. We investigated the roles of RIP140 and PGC-1alpha 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-1alpha, mediated through the binding of estrogen-related receptor alpha and NRF-1 to their cognate binding sites. Importantly, we demonstrate that RIP140 interacts directly with PGC-1alpha and suppresses its activity. The direct antagonism of PGC-1alpha by RIP140 provides a mechanism for regulating target gene transcription via nuclear receptor-dependent and -independent pathways.
Hallberg
Magnus
M
Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, Du Cane Road, London, United Kingdom W12 0NN.
Morganstein
Daniel L
DL
Kiskinis
Evangelos
E
Shah
Kunal
K
Kralli
Anastasia
A
Dilworth
Stephen M
SM
White
Roger
R
Parker
Malcolm G
MG
Christian
Mark
M
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D052437:Adipocytes, Brown / Q000166:cytology / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D008055:Lipids / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000078723:Nuclear Receptor Interacting Protein 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C112510:Cidea protein, mouse; D008055:Lipids; C000627127:NRIP1 protein, human; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors
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