Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of the circadian clock.
Article Details
- CitationCopy to clipboard
Yin L, Wang J, Klein PS, Lazar MA
Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of the circadian clock.
Science. 2006 Feb 17;311(5763):1002-5.
- PubMed ID
- 16484495 [ View in PubMed]
- Abstract
Lithium is commonly used to treat bipolar disorder, which is associated with altered circadian rhythm. Lithium is a potent inhibitor of glycogen synthase kinase 3 (GSK3), which regulates circadian rhythm in several organisms. In experiments with cultured cells, we show here that GSK3beta phosphorylates and stabilizes the orphan nuclear receptor Rev-erbalpha, a negative component of the circadian clock. Lithium treatment of cells leads to rapid proteasomal degradation of Rev-erbalpha and activation of clock gene Bmal1. A form of Rev-erbalpha that is insensitive to lithium interferes with the expression of circadian genes. Control of Rev-erbalpha protein stability is thus a critical component of the peripheral clock and a biological target of lithium therapy.