Publication Date:
2006-02-18
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yin, Lei -- Wang, Jing -- Klein, Peter S -- Lazar, Mitchell A -- DK 19525/DK/NIDDK NIH HHS/ -- DK45586/DK/NIDDK NIH HHS/ -- MH058324/MH/NIMH NIH HHS/ -- R01 MH058324/MH/NIMH NIH HHS/ -- R01 MH058324-07/MH/NIMH NIH HHS/ -- R01 MH058324-08/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2006 Feb 17;311(5763):1002-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Endocrinology, Diabetes, and Metabolism, and University of Pennsylvania School of Medicine, 415 Curie Boulevard, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16484495" target="_blank"〉PubMed〈/a〉
Keywords:
ARNTL Transcription Factors
;
Amino Acid Sequence
;
Animals
;
Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism
;
Biological Clocks/*physiology
;
Cell Line
;
Cell Line, Tumor
;
Circadian Rhythm/*physiology
;
DNA-Binding Proteins/chemistry/genetics/*metabolism
;
Down-Regulation
;
Gene Expression Regulation
;
Glycogen Synthase Kinase 3/antagonists & inhibitors/metabolism
;
Humans
;
Lithium Chloride/*pharmacology
;
Mice
;
Molecular Sequence Data
;
NIH 3T3 Cells
;
Nuclear Receptor Subfamily 1, Group D, Member 1
;
Phosphorylation
;
Promoter Regions, Genetic
;
Proteasome Endopeptidase Complex/metabolism
;
Proteasome Inhibitors
;
Receptors, Cytoplasmic and Nuclear/chemistry/genetics/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink