Bifunctional Role of Rev-erb alpha in Adipocyte Differentiation

Wang J, Lazar MA
Source: Mol Cell Biol
Publication Date: (2008)
Issue: 28(7): 2213-20
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
3T3-L1 pre-ad
Species: mouse
Tissue Origin: embryo
Nucleofectorâ„¢ I/II/2b
The nuclear receptor Rev-erbalpha is a potent transcriptional repressor that regulates circadian rhythm and metabolism. Here we demonstrate a dissociation between Rev-erbalpha mRNA and protein levels that profoundly influences adipocyte differentiation. During adipogenesis, Rev-erbalpha gene expression initially declines and subsequently increases. Remarkably, Rev-erbalpha protein levels are nearly opposite, increasing early in adipogenesis and then markedly decreasing in adipocytes. The Rev-erbalpha protein is necessary for the early mitotic events that are required for adipogenesis. The subsequent reduction in Rev-erbalpha protein, due to increased degradation via the 26S proteasome, is also required for adipocyte differentiation because Rev-erbalpha represses expression of PPARgamma2, the master transcriptional regulator of adipogenesis. Thus, opposite to what might be predicted from Rev-erbalpha gene expression, Rev-erbalpha protein levels must rise and then fall for adipocyte differentiation to occur.