CASEIN KINASE I: ANOTHER COG IN THE CIRCADIAN CLOCKWORKS

Abstract

Multiple components of the circadian central clock are phosphoproteins,and it has become increasingly clear that posttranslational modification isan important regulator of circadian rhythm in diverse organisms, from dinoflagellatesto humans. Genetic studies in Drosophilahave identified double-time (dbt), a serine/threonine protein kinase that is highlyhomologous to human casein kinase I epsilon (CKIε), as the first kinaselinked to behavioral rhythms. Identification of a missense mutation in CKIεas the tau mutation in the Syrian hamsterplaces CKIε within the core clock machinery in mammals. Most recently,identification of a phosphorylation site mutant of hPER2 in a family withan inherited circadian rhythm abnormality strongly suggests that PER2 is aphysiologically relevant substrate of CKI. Phosphorylation may regulate multipleproperties of clock proteins, including stability and intracellular localization.(Chronobiology International, 18(3), 389–398,2001)

• Casein kinase
• Circadian rhythm
• Double-time
• Phosphorylation