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

  • Authors:
    • Jan Kreutzer
    • Barbara Guerra
  • View Affiliations

  • Published online on: November 1, 2007     https://doi.org/10.3892/ijo.31.5.1251
  • Pages: 1251-1259
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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 β-subunit of protein kinase CK2. In the present study, ectopic expression of CK2β 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 CK2β expression. When degradation of CDC25A is induced by CK2β 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.

Related Articles

Journal Cover

November 2007
Volume 31 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Kreutzer, J., & Kreutzer, J. (2007). The regulatory β-subunit of protein kinase CK2 accelerates the degradation of CDC25A phosphatase through the checkpoint kinase Chk1. International Journal of Oncology, 31, 1251-1259. https://doi.org/10.3892/ijo.31.5.1251
MLA
Kreutzer, J., Guerra, B."The regulatory β-subunit of protein kinase CK2 accelerates the degradation of CDC25A phosphatase through the checkpoint kinase Chk1". International Journal of Oncology 31.5 (2007): 1251-1259.
Chicago
Kreutzer, J., Guerra, B."The regulatory β-subunit of protein kinase CK2 accelerates the degradation of CDC25A phosphatase through the checkpoint kinase Chk1". International Journal of Oncology 31, no. 5 (2007): 1251-1259. https://doi.org/10.3892/ijo.31.5.1251