NDLI: Nuclear Entry of the Circadian Regulator mPER1 Is Controlled by Mammalian Casein Kinase I ɛ

Content Provider	PubMed Central
Author	Vielhaber, Erica Eide, Erik Rivers, Ann Gao, Zhong-hua Virshup, David M.
Copyright Year	2000
Abstract	The molecular oscillator that keeps circadian time is generated by a negative feedback loop. Nuclear entry of circadian regulatory proteins that inhibit transcription from E-box-containing promoters appears to be a critical component of this loop in both Drosophila and mammals. The Drosophila double-time gene product, a casein kinase I ɛ (CKIɛ) homolog, has been reported to interact with dPER and regulate circadian cycle length. We find that mammalian CKIɛ binds to and phosphorylates the murine circadian regulator mPER1. Unlike both dPER and mPER2, mPER1 expressed alone in HEK 293 cells is predominantly a nuclear protein. Two distinct mechanisms appear to retard mPER1 nuclear entry. First, coexpression of mPER2 leads to mPER1-mPER2 heterodimer formation and cytoplasmic colocalization. Second, coexpression of CKIɛ leads to masking of the mPER1 nuclear localization signal and phosphorylation-dependent cytoplasmic retention of both proteins. CKIɛ may regulate mammalian circadian rhythm by controlling the rate at which mPER1 enters the nucleus.
Starting Page	4888
File Format	PDF
ISSN	10985549
e-ISSN	10985549
Journal	Molecular and Cellular Biology
Issue Number	13
Volume Number	20
Language	English
Publisher	American Society for Microbiology
Publisher Date	2000-07-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology

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Control of Intracellular Dynamics of Mammalian Period Proteins by Casein Kinase I ɛ (CKIɛ) and CKIδ in Cultured Cells

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