WAF1, a potential mediator of p53 tumor suppression
| Autor: | D Lin, Kenneth W. Kinzler, Takashi Tokino, W. Edward Mercer, Ramon Parsons, Jeffrey M. Trent, Daniel B. Levy, Bert Vogelstein, Victor E. Velculescu, Wafik S. El-Deiry |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Tumor suppressor gene Molecular Sequence Data Biology General Biochemistry Genetics and Molecular Biology Mice Gene interaction Cyclins Gene expression Animals Humans Enhancer trap Genes Tumor Suppressor Amino Acid Sequence RNA Messenger Cloning Molecular Promoter Regions Genetic DNA Primers Regulation of gene expression Reporter gene Base Sequence Cell Cycle Nuclear Proteins Nucleic Acid Hybridization Zinc Fingers CDKN1A Gene Molecular biology Rats Gene Expression Regulation Genes Suppression subtractive hybridization Chromosomes Human Pair 6 Tumor Suppressor Protein p53 |
| Zdroj: | Cell. 75:817-825 |
| ISSN: | 0092-8674 |
| Popis: | The ability of p53 to activate transcription from specific sequences suggests that genes induced by p53 may mediate its biological role as a tumor suppressor. Using a subtractive hybridization approach, we identified a gene, named WAF1, whose induction was associated with wild-type but not mutant p53 gene expression in a human brain tumor cell line. The WAF1 gene was localized to chromosome 6p21.2, and its sequence, structure, and activation by p53 was conserved in rodents. Introduction of WAF1 cDNA suppressed the growth of human brain, lung, and colon tumor cells in culture. Using a yeast enhancer trap, a p53-binding site was identified 2.4 kb upstream of WAF1 coding sequences. The WAF1 promoter, including this p53-binding site, conferred p53-dependent inducibility upon a heterologous reporter gene. These studies define a gene whose expression is directly induced by p53 and that could be an important mediator of p53-dependent tumor growth suppression. |
| Databáze: | OpenAIRE |
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