The phosphorylation switch that regulates ticking of the circadian clock.

Journal Article (Journal Article;Review)

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.

Full Text

Duke Authors

Cited Authors

  • Narasimamurthy, R; Virshup, DM

Published Date

  • March 18, 2021

Published In

Volume / Issue

  • 81 / 6

Start / End Page

  • 1133 - 1146

PubMed ID

  • 33545069

Electronic International Standard Serial Number (EISSN)

  • 1097-4164

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2021.01.006


  • eng

Conference Location

  • United States