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Molecular and Cellular Biology, April 2008, p. 2213-2220, Vol. 28, No. 7
0270-7306/08/$08.00+0     doi:10.1128/MCB.01608-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Bifunctional Role of Rev-erb{alpha} in Adipocyte Differentiation{triangledown}

Jing Wang and Mitchell A. Lazar*

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and Department of Genetics, and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Received 31 August 2007/ Returned for modification 9 October 2007/ Accepted 20 January 2008

The nuclear receptor Rev-erb{alpha} is a potent transcriptional repressor that regulates circadian rhythm and metabolism. Here we demonstrate a dissociation between Rev-erb{alpha} mRNA and protein levels that profoundly influences adipocyte differentiation. During adipogenesis, Rev-erb{alpha} gene expression initially declines and subsequently increases. Remarkably, Rev-erb{alpha} protein levels are nearly the opposite, increasing early in adipogenesis and then markedly decreasing in adipocytes. The Rev-erb{alpha} protein is necessary for the early mitotic events that are required for adipogenesis. The subsequent reduction in Rev-erb{alpha} protein, due to increased degradation via the 26S proteasome, is also required for adipocyte differentiation because Rev-erb{alpha} represses the expression of PPAR{gamma}2, the master transcriptional regulator of adipogenesis. Thus, opposite to what might be predicted from Rev-erb{alpha} gene expression, Rev-erb{alpha} protein levels must rise and then fall for adipocyte differentiation to occur.

* Corresponding author. Mailing address: University of Pennsylvania School of Medicine, 700 CRB, 415 Curie Blvd., Philadelphia, PA 19104-6149. Phone: (215) 898-0198. Fax: (215) 898-5408. E-mail: lazar{at}mail.med.upenn.edu

{triangledown} Published ahead of print on 28 January 2008.

Molecular and Cellular Biology, April 2008, p. 2213-2220, Vol. 28, No. 7
0270-7306/08/$08.00+0     doi:10.1128/MCB.01608-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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