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Publication : Casein kinase 1δ-dependent Wee1 protein degradation.

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.
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