TY - JOUR
T1 - Bifunctional role of Rev-erbα in adipocyte differentiation
AU - Wang, Jing
AU - Lazar, Mitchell A.
PY - 2008/4
Y1 - 2008/4
N2 - The nuclear receptor Rev-erbα is a potent transcriptional repressor that regulates circadian rhythm and metabolism. Here we demonstrate a dissociation between Rev-erbα mRNA and protein levels that profoundly influences adipocyte differentiation. During adipogenesis, Rev-erbα gene expression initially declines and subsequently increases. Remarkably, Rev-erbα protein levels are nearly the opposite, increasing early in adipogenesis and then markedly decreasing in adipocytes. The Rev-erbα protein is necessary for the early mitotic events that are required for adipogenesis. The subsequent reduction in Rev-erbα protein, due to increased degradation via the 26S proteasome, is also required for adipocyte differentiation because Rev-erbα represses the expression of PPARγ2, the master transcriptional regulator of adipogenesis. Thus, opposite to what might be predicted from Rev-erbα gene expression, Rev-erbα protein levels must rise and then fall for adipocyte differentiation to occur.
AB - The nuclear receptor Rev-erbα is a potent transcriptional repressor that regulates circadian rhythm and metabolism. Here we demonstrate a dissociation between Rev-erbα mRNA and protein levels that profoundly influences adipocyte differentiation. During adipogenesis, Rev-erbα gene expression initially declines and subsequently increases. Remarkably, Rev-erbα protein levels are nearly the opposite, increasing early in adipogenesis and then markedly decreasing in adipocytes. The Rev-erbα protein is necessary for the early mitotic events that are required for adipogenesis. The subsequent reduction in Rev-erbα protein, due to increased degradation via the 26S proteasome, is also required for adipocyte differentiation because Rev-erbα represses the expression of PPARγ2, the master transcriptional regulator of adipogenesis. Thus, opposite to what might be predicted from Rev-erbα gene expression, Rev-erbα protein levels must rise and then fall for adipocyte differentiation to occur.
UR - http://www.scopus.com/inward/record.url?scp=41149132147&partnerID=8YFLogxK
U2 - 10.1128/MCB.01608-07
DO - 10.1128/MCB.01608-07
M3 - Article
C2 - 18227153
AN - SCOPUS:41149132147
VL - 28
SP - 2213
EP - 2220
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 7
ER -