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.
Artigo
em Inglês
| WPRIM
| ID: wpr-115205
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fosforilação
/
Fosfotransferases
/
Fatores de Transcrição
/
Nações Unidas
/
Dano ao DNA
/
Ciclo Celular
/
Linhagem Celular
/
Western Blotting
/
Fase G2
/
Proteína Quinase CDC2
Limite:
Humanos
Idioma:
Inglês
Revista:
Cancer Research and Treatment
Ano de publicação:
2006
Tipo de documento:
Artigo
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