| Reverse orientation c-erbA gene α (Rev-erbα, EAR-1, or NR1D1) is a widely expressed member of the orphan nuclear receptor family of proteins (1). Rev-erbα is highly expressed in adipose tissue, skeletal muscle, brain and liver, and regulates cellular proliferation and differentiation. Expression increases during differentiation in adipocytes and ectopic expression of Rev-erbα potentiates the adipocyte differentiation of 3T3-L1 cells (2). In addition, expression oscillates with circadian rhythm in liver cells and Rev-erbα regulates expression of BMAL1, ApoA-I and ApoC-III, all key regulators of circadian rhythm (3-7). Phosphorylation of Rev-erbα Ser55 and Ser59 by GSK-3β appears to stabilize Rev-erbα protein levels and is important for synchronizing and maintaining the circadian clock (8). Rev-erbα also regulates inflammation by targeting the NF-κB responsive genes IL-6 and COX-2 (9). Rev-erbα lacks the activation function 2 domain required for ligand-dependent activation of transcription by other members of the nuclear receptor family; thus it behaves as a constitutive repressor protein, recruiting the nuclear receptor co-repressor (N-CoR)/HDAC3 complex to target genes to repress transcription (10). |
