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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Yang, Vincent W. Yoon, Hong S. Chen, Xinming |
| Description | Author Affiliation: Yoon HS ( Division of Digestive Diseases, Department of Medicine and Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA.) |
| Abstract | The tumor suppressor p53 is required for the maintenance of genomic integrity following DNA damage. One mechanism by which p53 functions is to induce a block in the transition between the G(1) and S phase of the cell cycle. Previous studies indicate that the Krüppel-like factor 4 (KLF4) gene is activated following DNA damage and that such activation depends on p53. In addition, enforced expression of KLF4 causes G(1)/S arrest. The present study examines the requirement of KLF4 in mediating the p53-dependent cell cycle arrest process in response to DNA damage. We show that the G(1) population of a colon cancer cell line, HCT116, that is null for the p53 alleles (-/-) was abolished following gamma irradiation compared with cells with wild-type p53 (+/+). Conditional expression of KLF4 in irradiated HCT116 p53-/- cells restored the G(1) cell population to a level similar to that seen in irradiated HCT116 p53+/+ cells. Conversely, treatment of HCT116 p53+/+ cells with small interfering RNA (siRNA) specific for KLF4 significantly reduced the number of cells in the G(1) phase following gamma irradiation compared with the untreated control or those treated with a nonspecific siRNA. In each case the increase or decrease in KLF4 level because of conditional induction or siRNA inhibition, respectively, was accompanied by an increase or decrease in the level of p21(WAF1/CIP1). Results of our study indicate that KLF4 is an essential mediator of p53 in controlling G(1)/S progression of the cell cycle following DNA damage. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 4 |
| Volume Number | 278 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2003-01-24 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | DNA Damage DNA-Binding Proteins Physiology G1 Phase S Phase Transcription Factors Tumor Suppressor Protein P53 Metabolism Adenoviridae Genetics Blotting, Western Cell Cycle Cyclin-Dependent Kinase Inhibitor P21 Cyclins Biosynthesis Gamma Rays Kruppel-Like Transcription Factors Transfection Tumor Cells, Cultured Research Support, U.S. Gov't, P.H.S. Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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