Casein Kinase 1{delta} Dependent Wee1 Degradation [Signal Transduction]

May 9th, 2014 by Penas, C., Ramachandran, V., Simanski, S., Lee, C., Madoux, F., Rahaim, R. J., Chauhan, R., Barnaby, O., Schurer, S., Hodder, P., Steen, J., Roush, W. R., Ayad, N. G.

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 CK1δ dependent Wee1 degradation. Small molecule CK1δ inhibitors specifically disrupted Wee1 destruction and arrested HeLa cell proliferation. Pharmacological inhibition, siRNA knockdown, or conditional deletion of CK1δ also reduced Wee1 turnover. These studies thus define a previously unappreciated role for CK1δ in controlling the cell cycle.