Nuclear Receptor Rev-erbα Is a Critical Lithium-Sensitive Component of the Circadian Clock

@article{Yin2006NuclearRR,
  title={Nuclear Receptor Rev-erb$\alpha$ Is a Critical Lithium-Sensitive Component of the Circadian Clock},
  author={Lei Yin and Jing Wang and Peter S Klein and Mitchell A. Lazar},
  journal={Science},
  year={2006},
  volume={311},
  pages={1002 - 1005}
}
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 GSK3β phosphorylates and stabilizes the orphan nuclear receptor Rev-erbα, a negative component of the circadian clock. Lithium treatment of cells leads to rapid proteasomal degradation of Rev-erbα and activation of… 
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TLDR
It is found that lithium significantly increased the expression of Per2 and Cry1, whereas Per3, Cry2, Bmal1, E4BP4 and Rev-Erb-α expression was reduced, and lithium prolonged the period of Per1 and Per2.
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TLDR
These findings establish the two Rev-erbs as major regulators of both clock function and metabolism, displaying a level of subtype collaboration that is unusual among nuclear receptors but common among core clock proteins, protecting the organism from major perturbations in circadian and metabolic physiology.
Rev-erbalpha2 mRNA encodes a stable protein with a potential role in circadian clock regulation.
TLDR
It is proposed that the relative expression levels of the two REV-ERBalpha variants fine-tune the circadian period length by regulating REV-, rev-erbalpha1 and alpha2 half-life.
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