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

Neuroreport. 2000 Apr 7;11(5):951-5. doi: 10.1097/00001756-200004070-00011.


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.

MeSH terms

  • Animals
  • CLOCK Proteins
  • Casein Kinases
  • Cell Cycle Proteins
  • Cells, Cultured
  • Circadian Rhythm / physiology
  • Drosophila Proteins*
  • Fetus
  • Genetic Vectors
  • Humans
  • Nuclear Proteins / metabolism*
  • Period Circadian Proteins
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Transcription Factors / metabolism


  • Cell Cycle Proteins
  • Clk protein, Drosophila
  • Drosophila Proteins
  • Nuclear Proteins
  • PER1 protein, human
  • Period Circadian Proteins
  • Transcription Factors
  • CLOCK Proteins
  • Protein Kinases
  • Casein Kinases