title: The regulatory beta-subunit of protein kinase CK2 accelerates the degradation of CDC25A phosphatase through the checkpoint kinase Chk1.
abstract: Human CDC25 phosphatases play an important role in cell cycle regulation by removing inhibitory phosphate groups on cyclin-CDKs. Chk1 has been shown to phosphorylate CDC25 family members down-regulating their phosphatase activity through distinct mechanisms. The kinase activity of Chk1 is evident in unperturbed cells and becomes enhanced in response to DNA damage or stalled replication. We have previously shown that the activity of Chk1 is increased following interaction with the regulatory beta-subunit of protein kinase CK2. In the present study, ectopic expression of CK2beta 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 Chk1, we demonstrate that Chk1 mediates the down-regulation of endogenous CDC25A, which occurs upon induction of CK2beta expression. When degradation of CDC25A is induced by CK2beta during activation of the G2 checkpoint, it leads to partial dephosphorylation of Cdc2 at its inhibitory residue Tyr15. 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 Chk1 in the absence of DNA damage.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Kreutzer
authors.forename: Barbara
authors.initials: B
authors.lastname: Guerra
mesh_terms: D047390:Casein Kinase II / Q000502:physiology*; D002453:Cell Cycle; D000071877:Checkpoint Kinase 1; D004249:DNA Damage; D006801:Humans; D011494:Protein Kinases / Q000502:physiology*; D020687:cdc25 Phosphatases / Q000378:metabolism*
chemical_list: D011494:Protein Kinases; C000605867:CHEK1 protein, human; D047390:Casein Kinase II; D000071877:Checkpoint Kinase 1; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases