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period of the circadian oscillator is primarily determined by the balance between casein kinase 1 and protein phosphatase 1.

Title: The period of the circadian oscillator is primarily determined by the balance between casein kinase 1 and protein phosphatase 1.
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Name(s): Lee, Hyeong-min, author
Chen, Rongmin, author
Kim, Hyukmin, author
Etchegaray, Jean-Pierre, author
Weaver, David R, author
Lee, Choogon, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2011-09-27
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Mounting evidence suggests that PERIOD (PER) proteins play a central role in setting the speed (period) and phase of the circadian clock. Pharmacological and genetic studies have shown that changes in PER phosphorylation kinetics are associated with changes in circadian rhythm period and phase, which can lead to sleep disorders such as Familial Advanced Sleep Phase Syndrome in humans. We and others have shown that casein kinase 1δ and ε (CK1δ/ε) are essential PER kinases, but it is clear that additional, unknown mechanisms are also crucial for regulating the kinetics of PER phosphorylation. Here we report that circadian periodicity is determined primarily through PER phosphorylation kinetics set by the balance between CK1δ/ε and protein phosphatase 1 (PP1). In CK1δ/ε-deficient cells, PER phosphorylation is severely compromised and nonrhythmic, and the PER proteins are constitutively cytoplasmic. However, when PP1 is disrupted, PER phosphorylation is dramatically accelerated; the same effect is not seen when PP2A is disrupted. Our work demonstrates that the speed and rhythmicity of PER phosphorylation are controlled by the balance between CK1δ/ε and PP1, which in turn determines the period of the circadian oscillator. Thus, our findings provide clear insights into the molecular basis of how the period and phase of our daily rhythms are determined.
Identifier: FSU_pmch_21930935 (IID), 10.1073/pnas.1107178108 (DOI), PMC3182690 (PMCID), 21930935 (RID), 21930935 (EID), 1107178108 (PII)
Grant Number: R01 NS053616, R01 NS056125, NS-053616, NS-056125
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182690.
Subject(s): Animals
Casein Kinase I/metabolism
Circadian Rhythm
Electrophoresis, Polyacrylamide Gel
Mice
Period Circadian Proteins/metabolism
Period Circadian Proteins/physiology
Phosphorylation
Protein Phosphatase 1/metabolism
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_21930935
Owner Institution: FSU
Is Part Of: Proceedings of the National Academy of Sciences of the United States of America.
1091-6490
Issue: iss. 39, vol. 108

Choose the citation style.
Lee, H. -min, Chen, R., Kim, H., Etchegaray, J. -P., Weaver, D. R., & Lee, C. (2011). The period of the circadian oscillator is primarily determined by the balance between casein kinase 1 and protein phosphatase 1. Proceedings Of The National Academy Of Sciences Of The United States Of America. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_21930935