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

Feb 18, 2006Science (New York, N.Y.)

The cellular switch Rev-erbalpha is an important lithium-sensitive part of the body’s daily clock

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Abstract

Lithium treatment leads to rapid degradation of Rev-erbalpha, a key regulator of the circadian clock.

  • GSK3beta phosphorylates and stabilizes Rev-erbalpha, influencing circadian rhythm.
  • Lithium inhibits GSK3, resulting in decreased levels of Rev-erbalpha.
  • The degradation of Rev-erbalpha activates the expression of the clock gene Bmal1.
  • A lithium-insensitive form of Rev-erbalpha disrupts the expression of circadian genes.
  • Rev-erbalpha protein stability is essential for the proper functioning of the peripheral circadian clock.

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