First Author | Penas C | Year | 2014 |
Journal | J Biol Chem | Volume | 289 |
Issue | 27 | Pages | 18893-903 |
PubMed ID | 24817118 | Mgi Jnum | J:216028 |
Mgi Id | MGI:5607502 | Doi | 10.1074/jbc.M114.547661 |
Citation | Penas C, et al. (2014) Casein kinase 1delta-dependent Wee1 protein degradation. J Biol Chem 289(27):18893-903 |
abstractText | Eukaryotic mitotic entry is controlled by Cdk1, which is activated by the Cdc25 phosphatase and inhibited by Wee1 tyrosine kinase, a target of the ubiquitin proteasome pathway. Here we use a reporter of Wee1 degradation, K328M-Wee1-luciferase, to screen a kinase-directed chemical library. Hit profiling identified CK1delta-dependent Wee1 degradation. Small-molecule CK1delta inhibitors specifically disrupted Wee1 destruction and arrested HeLa cell proliferation. Pharmacological inhibition, siRNA knockdown, or conditional deletion of CK1delta also reduced Wee1 turnover. Thus, these studies define a previously unappreciated role for CK1delta in controlling the cell cycle. |