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

Casein kinase Iϵ (CKIϵ), 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 CKIϵ causes a shortened circadian period in Syrian Golden hamster. We have now extended our previous studies to show that human casein kinase Iδ (hCKIδ), the closest homologue to hCKIϵ, associates with and phosphorylates hPER1 and causes protein instability. Furthermore, we observed that both hCKIδ and hCKIϵ phosphorylated and caused protein instability of human period 2 protein (hPER2). Immunohistochemical staining of rat brains demonstrates that CKIδ protein is localized in the suprachiasmatic nuclei, the central location of the master clock. These results indicate that CKIδ may play a role similar to CKIϵ, suggesting that it may also be involved in regulating circadian rhythmicity by post-translation modification of mammalian clock proteins hPER1 and 2.