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Stoichiometric relationship among clock proteins determines robustness of circadian rhythms.

Title: Stoichiometric relationship among clock proteins determines robustness of circadian rhythms.
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Name(s): Lee, Yongjin, author
Chen, Rongmin, author
Lee, Hyeong-min, author
Lee, Choogon, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2011-03-04
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: The mammalian circadian oscillator is primarily driven by an essential negative feedback loop comprising a positive component, the CLOCK-BMAL1 complex, and a negative component, the PER-CRY complex. Numerous studies suggest that feedback inhibition of CLOCK-BMAL1 is mediated by time-dependent physical interaction with its direct target gene products PER and CRY, suggesting that the ratio between the negative and positive complexes must be important for the molecular oscillator and rhythm generation. We explored this idea by altering expression of clock components in fibroblasts derived from Per2(Luc) and Per mutant mice, a cell system extensively used to study in vivo clock mechanisms. Our data demonstrate that the stoichiometric relationship between clock components is critical for the robustness of circadian rhythms and provide insights into the mechanistic organization of the negative feedback loop. Our findings may explain why certain mutant mice or cells are arrhythmic, whereas others are rhythmic, and suggest that robustness of circadian rhythms can be increased even in wild-type cells by modulating the stoichiometry.
Identifier: FSU_pmch_21199878 (IID), 10.1074/jbc.M110.207217 (DOI), PMC3044960 (PMCID), 21199878 (RID), 21199878 (EID), M110.207217 (PII)
Grant Number: R01 NS053616, NS-053616
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044960.
Subject(s): ARNTL Transcription Factors/genetics
ARNTL Transcription Factors/metabolism
Animals
CLOCK Proteins/genetics
CLOCK Proteins/metabolism
COS Cells
Cercopithecus aethiops
Circadian Rhythm/physiology
Circadian Rhythm Signaling Peptides and Proteins/genetics
Circadian Rhythm Signaling Peptides and Proteins/metabolism
Cryptochromes/genetics
Cryptochromes/metabolism
Feedback, Physiological/physiology
Fibroblasts/cytology
Fibroblasts/physiology
Gene Expression Regulation/physiology
Mice
Period Circadian Proteins/genetics
Period Circadian Proteins/metabolism
Promoter Regions, Genetic/physiology
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_21199878
Owner Institution: FSU
Is Part Of: The Journal of biological chemistry.
1083-351X
Issue: iss. 9, vol. 286

Choose the citation style.
Lee, Y., Chen, R., Lee, H. -min, & Lee, C. (2011). Stoichiometric relationship among clock proteins determines robustness of circadian rhythms. The Journal Of Biological Chemistry. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_21199878