p53 Prevents Immature Escaping from Cell Cycle G2 Checkpoint Arrest through Inhibiting cdk2-dependent NF-Y Phosphorylation.
- Author:
Un Jung YUN
1
;
Heui Dong PARK
;
Deug Y SHIN
Author Information
1. National Research Laboratory of Cell Cycle Regulation, Department of Microbiology, Dankook University College of Medicine, Cheonan, Korea. dreamer@dku.edu
- Publication Type:Original Article
- Keywords:
Tumor suppressor protein p53;
Cell cycle;
G2 phase;
Cdc2 protein kinase;
NF-Y protein
- MeSH:
Blotting, Western;
CCAAT-Binding Factor;
CDC2 Protein Kinase;
Cell Cycle Checkpoints;
Cell Cycle*;
Cell Death;
Cell Line;
Colonic Neoplasms;
Cyclin B;
DNA Damage;
G2 Phase;
Humans;
Immunoprecipitation;
Mitosis;
Phosphorylation*;
Phosphotransferases;
Transcription Factors;
Tumor Suppressor Protein p53;
United Nations*
- From:Cancer Research and Treatment
2006;38(4):224-228
- CountryRepublic of Korea
- Language:English
-
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. CONCLUSION: 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-rgulatory genes, including cdc2 and cyclin B.
