Phosphorylation and destabilization of human period I clock protein by human casein kinase I epsilon.
Published
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
Language
- eng
Conference Location
- England