气候变化领域集成服务门户(CCPortal): Molecular mechanism of the repressive phase of the mammalian circadian clock

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DOI	10.1073/pnas.2021174118
	Molecular mechanism of the repressive phase of the mammalian circadian clock
	Cao X.; Yang Y.; Selby C.P.; Liu Z.; Sancar A.
发表日期	2021
ISSN	00278424
卷号	118 期号:2
英文摘要	The mammalian circadian clock consists of a transcription–translation feedback loop (TTFL) composed of CLOCK–BMAL1 transcriptional activators and CRY–PER transcriptional repressors. Previous work showed that CRY inhibits CLOCK–BMAL1-activated transcription by a “blocking”-type mechanism and that CRY–PER inhibits CLOCK–BMAL1 by a “displacement”-type mechanism. While the mechanism of CRY-mediated repression was explained by both in vitro and in vivo experiments, the CRY–PER-mediated repression in vivo seemed in conflict with the in vitro data demonstrating PER removes CRY from the CLOCK–BMAL1–E-box complex. Here, we show that CRY–PER participates in the displacement-type repression by recruiting CK1δ to the nucleus and mediating an increased local concentration of CK1δ at CLOCK–BMAL1-bound promoters/enhancers and thus promoting the phosphorylation of CLOCK and dissociation of CLOCK–BMAL1 along with CRY from the E-box. Our findings bring clarity to the role of PER in the dynamic nature of the repressive phase of the TTFL. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Casein kinase; Circadian clock; Cryptochrome; DNA binding proteins; Period
语种	英语
scopus关键词	carrier proteins and binding proteins; casein kinase; CK1delta protein; transcription factor; transcription factor ARNTL; transcription factor CLOCK; transcription factor CRY; transcription factor PER; unclassified drug; Article; cell nucleus; circadian rhythm; complex formation; enhancer region; feedback system; gel mobility shift assay; genetic transcription; priority journal; promoter region; protein domain; protein function; protein localization; protein phosphorylation; RNA translation
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181099
作者单位	Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill, NC 27599-7260, United States
推荐引用方式 GB/T 7714	Cao X.,Yang Y.,Selby C.P.,et al. Molecular mechanism of the repressive phase of the mammalian circadian clock[J],2021,118(2).
APA	Cao X.,Yang Y.,Selby C.P.,Liu Z.,&Sancar A..(2021).Molecular mechanism of the repressive phase of the mammalian circadian clock.Proceedings of the National Academy of Sciences of the United States of America,118(2).
MLA	Cao X.,et al."Molecular mechanism of the repressive phase of the mammalian circadian clock".Proceedings of the National Academy of Sciences of the United States of America 118.2(2021).