Your browser doesn't support javascript.
loading
The phosphorylation switch that regulates ticking of the circadian clock.
Narasimamurthy, Rajesh; Virshup, David M.
Afiliação
  • Narasimamurthy R; Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore. Electronic address: rajesh.n@duke-nus.edu.sg.
  • Virshup DM; Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore; Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: david.virshup@duke-nus.edu.sg.
Mol Cell ; 81(6): 1133-1146, 2021 03 18.
Article em En | MEDLINE | ID: mdl-33545069
In our 24/7 well-lit world, it's easy to skip or delay sleep to work, study, and play. However, our circadian rhythms are not easily fooled; the consequences of jet lag and shift work are many and severe, including metabolic, mood, and malignant disorders. The internal clock that keeps track of time has at its heart the reversible phosphorylation of the PERIOD proteins, regulated by isoforms of casein kinase 1 (CK1). In-depth biochemical, genetic, and structural studies of these kinases, their mutants, and their splice variants have combined over the past several years to provide a robust understanding of how the core clock is regulated by a phosphoswitch whereby phosphorylation of a stabilizing site on PER blocks phosphorylation of a distant phosphodegron. The recent structure of a circadian mutant form of CK1 implicates an internal activation loop switch that regulates this phosphoswitch and points to new approaches to regulation of the clock.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ritmo Circadiano / Caseína Quinase I / Proteínas Circadianas Period / Relógios Circadianos Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ritmo Circadiano / Caseína Quinase I / Proteínas Circadianas Period / Relógios Circadianos Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article