p53 Prevents Immature Escaping from Cell Cycle G2 Checkpoint Arrest through Inhibiting cdk2-dependent NF-Y Phosphorylation / Journal of the Korean Cancer Association, 대한암학회지
Cancer Research and Treatment
; : 224-228, 2006.
Article
in En
| WPRIM
| ID: wpr-115205
Responsible library:
WPRO
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 ANDMETHODS:
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.Key words
Full text:
1
Index:
WPRIM
Main subject:
Phosphorylation
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Phosphotransferases
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Transcription Factors
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United Nations
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DNA Damage
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Cell Cycle
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Cell Line
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Blotting, Western
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G2 Phase
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CDC2 Protein Kinase
Limits:
Humans
Language:
En
Journal:
Cancer Research and Treatment
Year:
2006
Type:
Article