Nuclear entry of the circadian regulator MPER1 is controlled by mammalian casein kinase I ε

Erica Vielhaber, Erik Eide, Ann Rivers, Zhong Hua Gao, David M. Virshup

Research output: Contribution to journalArticlepeer-review

247 Scopus citations


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 ε (CKIε) homolog, has been reported to interact with dPER and regulate circadian cycle length. We find that mammalian CKIε 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 CKIε leads to masking of the mPER1 nuclear localization signal and phosphorylation-dependent cytoplasmic retention of both proteins. CKIε may regulate mammalian circadian rhythm by controlling the rate at which mPER1 enters the nucleus.

Original languageEnglish (US)
Pages (from-to)4888-4899
Number of pages12
JournalMolecular and cellular biology
Issue number13
StatePublished - Jul 2000

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


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