Phosphorylation and destabilization of human period I clock protein by human casein kinase I epsilon.
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Keesler GA, Camacho F, Guo Y, Virshup D, Mondadori C, Yao Z
Phosphorylation and destabilization of human period I clock protein by human casein kinase I epsilon.
Neuroreport. 2000 Apr 7;11(5):951-5.
- PubMed ID
- 10790862 [ View in PubMed]
- Abstract
Period (PER), a central component of the circadian clock in Drosophila, undergoes daily oscillation in abundance and phosphorylation state. Here we report that human casein kinase I epsilon (hCKI epsilon) can phosphorylate human PER I (hPER I). Purified recombinant hCKI epsilon (but not a kinase negative mutant of hCKI epsilon, hCKI epsilon-K38R) phosphorylated hPER I in vitro. When co-transfected with wild-type hCKI epsilon, in 293T cells, hPER I showed a significant increase in phosphorylation as evidenced by a shift in molecular mass. Furthermore, phosphorylation of hPER I by hCKI epsilon caused a decrease in protein stability in hPER I. Whereas phosphorylated hPER I had a half-life of approximately 12 h, unphosphorylated hPER I remained stable in the cell for > 24 h. hPER I protein could also be co-immunoprecipitated with transfected hCKI epsilon as well as endogenous hCKI epsilon, indicating physical association between hPER I and hCKI epsilon proteins in vivo.