| Autor: |
Vielhaber, Erica, Eide, Erik, Rivers, Ann, Gao, Zhong-Hua, Virshup, David M. |
| Zdroj: |
Molecular and Cellular Biology; July 2000, Vol. 20 Issue: 13 p4888-4899, 12p |
| Abstrakt: |
ABSTRACTThe 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 bothDrosophilaand mammals. The Drosophila double-timegene product, a casein kinase I ? (CKI?) homolog, has been reported to interact with dPER and regulate circadian cycle length. We find that mammalian CKI? 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 CKI? leads to masking of the mPER1 nuclear localization signal and phosphorylation-dependent cytoplasmic retention of both proteins. CKI? may regulate mammalian circadian rhythm by controlling the rate at which mPER1 enters the nucleus. |
| Databáze: |
Supplemental Index |
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