Phosphorylation and destabilization of human period I clock protein by human casein kinase I epsilon.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Keesler, GA; Camacho, F; Guo, Y; Virshup, D; Mondadori, C; Yao, Z

Published Date

  • April 7, 2000

Published In

Volume / Issue

  • 11 / 5

Start / End Page

  • 951 - 955

PubMed ID

  • 10790862

Pubmed Central ID

  • 10790862

International Standard Serial Number (ISSN)

  • 0959-4965

Digital Object Identifier (DOI)

  • 10.1097/00001756-200004070-00011


  • eng

Conference Location

  • England