Display options
Cite
Yun UJ, Park HD, Shin DY. p53 prevents immature escaping from cell cycle G2 checkpoint arrest through inhibiting cdk2-dependent NF-Y phosphorylation. Cancer Res Treat. 2006;38(4):224-8doi: 10.4143/crt.2006.38.4.224.
Yun, U. J., Park, H. D., & Shin, D. Y. (2006). p53 prevents immature escaping from cell cycle G2 checkpoint arrest through inhibiting cdk2-dependent NF-Y phosphorylation. Cancer research and treatment, 38(4), 224-8. https://doi.org/10.4143/crt.2006.38.4.224
Yun, Un-Jung, et al. "p53 prevents immature escaping from cell cycle G2 checkpoint arrest through inhibiting cdk2-dependent NF-Y phosphorylation." Cancer research and treatment vol. 38,4 (2006): 224-8. doi: https://doi.org/10.4143/crt.2006.38.4.224
Yun UJ, Park HD, Shin DY. p53 prevents immature escaping from cell cycle G2 checkpoint arrest through inhibiting cdk2-dependent NF-Y phosphorylation. Cancer Res Treat. 2006 Dec;38(4):224-8. doi: 10.4143/crt.2006.38.4.224. Epub 2006 Dec 31. PMID: 19771247; PMCID: PMC2741649.
Copy Download .nbib Format: NLM
Share it on

Cancer Res Treat. 2006 Dec;38(4):224-8. doi: 10.4143/crt.2006.38.4.224. Epub 2006 Dec 31.

p53 prevents immature escaping from cell cycle G2 checkpoint arrest through inhibiting cdk2-dependent NF-Y phosphorylation.

Cancer research and treatment

Un-Jung Yun, Heui-Dong Park, Deug Y Shin

Affiliations

  1. National Research Laboratory of Cell Cycle Regulation, Department of Microbiology, Dankook University College of Medicine, Cheonan, Korea.

PMID: 19771247 PMCID: PMC2741649 DOI: 10.4143/crt.2006.38.4.224

Abstract

PURPOSE: Recent studies have suggested that p53 regulates the G2 checkpoint in the cell cycle and this function is required for the maintenance of genomic integrity. In this study, we addressed a role of p53 in escaping from cell cycle G2 arrest following DNA damage.

MATERIALS AND METHODS: Cell cycle checkpoint arrest in the human colon cancer cell line HCT116 and its derivatives carry p53 or p21 deletions, were examined by FACS analysis, immunoprecipitation, Western blot and IP-kinase assay.

RESULTS: While the cells with functional p53 were arrested at both the G1 and G2 checkpoints, the p53-deficient cells failed to arrest at G1, but they were arrested at G2. However, the p53-deficient cells failed to sustain G2 checkpoint arrest and they entered mitosis earlier than did the p53-positive cells and so this resulted in extensive cell death. Cdc2 kinase becomes reactivated in p53-deficient cells in association with entry into mitosis, but not in the p53-positive cells. Upon DNA damage, the p21-deficient cells, like the p53-negative cells, not only failed to repress cdk2-dependent NF-Y phosphorylation, but they also failed to repress the expression of such cell cycle G2-regulatory genes as cdc2, cyclin B, RNR-R2 and cdc25C, which have all been previously reported as targets of NF-Y transcription factor.

CONCLUSIONS: p53 is essential to prevent immature escaping from cell cycle G2 checkpoint arrest through p21-mediated cdk2 inactivation, and this leads to inhibition of cdk2-dependent NF-Y phosphorylation and NF-Y dependent transcription of the cell cycle G2-regulatory genes, including cdc2 and cyclin B.

Keywords: Cdc2 protein kinase; Cell cycle; G2 phase; NF-Y protein; Tumor suppressor protein p53

References

  1. Oncogene. 2001 Sep 13;20(41):5818-25 - PubMed
  2. Nature. 1996 Jun 20;381(6584):713-6 - PubMed
  3. Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9648-53 - PubMed
  4. Science. 1989 Nov 3;246(4930):629-34 - PubMed
  5. Science. 1998 Nov 20;282(5393):1497-501 - PubMed
  6. Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8493-7 - PubMed
  7. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7491-5 - PubMed
  8. Cell. 1993 Nov 19;75(4):817-25 - PubMed
  9. Oncogene. 2004 May 20;23(23):4084-8 - PubMed
  10. Science. 1991 Jul 5;253(5015):49-53 - PubMed
  11. Cancer Res. 2000 Feb 1;60(3):542-5 - PubMed
  12. Virology. 1973 Aug;54(2):536-9 - PubMed
  13. J Biol Chem. 2003 Sep 19;278(38):36966-72 - PubMed
  14. J Biol Chem. 2001 Feb 23;276(8):5570-6 - PubMed
  15. J Biol Chem. 1999 Oct 15;274(42):29677-82 - PubMed

Publication Types