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Molecular and Cellular Biology, November 2008, p. 6785-6795, Vol. 28, No. 22
0270-7306/08/$08.00+0     doi:10.1128/MCB.00504-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Functional Interaction between RIP140 and PGC-1{alpha} Regulates the Expression of the Lipid Droplet Protein CIDEA{triangledown} ,{dagger}

Magnus Hallberg,1 Daniel L. Morganstein,1 Evangelos Kiskinis,1 Kunal Shah,1 Anastasia Kralli,2 Stephen M. Dilworth,1 Roger White,1 Malcolm G. Parker,1* and Mark Christian1

Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, Du Cane Road, London, United Kingdom W12 0NN,1 Department of Cell Biology, The Scripps Research Institute, La Jolla, California 920372

Received 28 March 2008/ Returned for modification 23 April 2008/ Accepted 2 September 2008

Nuclear receptors activate or repress target genes depending on the recruitment of coactivators or corepressors. The corepressor RIP140 and the PPAR coactivator 1{alpha} (PGC-1{alpha}) both play key roles in the regulated transcription of genes involved in energy homeostasis. We investigated the roles of RIP140 and PGC-1{alpha} 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-1{alpha}, 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-1{alpha} and suppresses its activity. The direct antagonism of PGC-1{alpha} by RIP140 provides a mechanism for regulating target gene transcription via nuclear receptor-dependent and -independent pathways.


* Corresponding author. Mailing address: Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, Du Cane Road, London, United Kingdom W12 0NN. Phone: 44 2075942177. Fax: 44 2075942184. E-mail: m.parker{at}imperial.ac.uk

{triangledown} Published ahead of print on 15 September 2008.

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


Molecular and Cellular Biology, November 2008, p. 6785-6795, Vol. 28, No. 22
0270-7306/08/$08.00+0     doi:10.1128/MCB.00504-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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