The regulatory β-subunit of protein kinase CK2 accelerates the degradation of CDC25A phosphatase through the checkpoint kinase Chk1

Human CDC25 phosphatases play an important role in cell cycle regulation by removing inhibitory phosphate groups on cyclin-CDKs. Chkl has been shown to phosphorylate CDC25 family members down-regulating their phosphatase activity through distinct mechanisms. The kinase activity of Chkl is evident in unperturbed cells and becomes enhanced in response to DNA damage or stalled replication. We have previously shown that the activity of Chkl is increased following interaction with the regulatory s-subunit of protein kinase CK2. In the present study, ectopic expression of CK2B during normal cell cycle progression is shown to enhance CDC25A degradation, and this occurs in a manner similar to that by which CDC25A is down-regulated upon activation of cellular checkpoint responses. By using RNA interference to specifically deplete cells of Chkl, we demonstrate that Chkl mediates the down-regulation of endogenous CDC25A, which occurs upon induction of CK2B expression. When degradation of CDC25A is induced by CK2B during activation of the G2 checkpoint, it leads to partial dephosphorylation of Cdc2 at its inhibitory residue Tyrl5. These results suggest that protein kinase CK2 is involved in cell cycle regulation and indicate the mechanism by which CDC25A turnover might be regulated by Chkl in the absence of DNA damage.