Human casein kinase Iδ phosphorylation of human circadian clock proteins period 1 and 2

Casein kinase I epsilon (CKI epsilon), a central component of the circadian clock, interacts with and phosphorylates human period protein 1 (hPER1) [Keesler, G.A. et al, (2000) NeuroReport 5, 951-955]. A mutation in CKI epsilon causes a shortened circadian period in Syrian Golden hamster. We have now extended our previous studies to show that human casein kinase 1 delta (hCKI delta), the closest homologue to hCKI epsilon, associates with and phosphorylates hPER1 and causes protein instability. Furthermore, we observed that both hCKI delta and hCKI epsilon phosphorylated and caused protein instability of human period 2 protein (hPER2), Immunohistochemical staining of rat brains demonstrates that CRI delta protein is localized in the suprachiasmatic nuclei, the central location of the master clock. These results indicate that CKI delta may play a role similar to CKI epsilon, suggesting that it may also be involved in regulating circadian rhythmicity by post-translation modification of mammalian clock proteins hPER1 and 2, (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.