WAF1, A POTENTIAL MEDIATOR OF P53 TUMOR SUPPRESSION
WAF1, A POTENTIAL MEDIATOR OF P53 TUMOR SUPPRESSION
复制标题
DOI：
10.1016/0092-8674(93)90500-p
复制
发表时间：
1993-11-19
期刊：
影响因子：
64.5
通讯作者：
VOGELSTEIN, B
中科院分区：
文献类型：
--
作者：
ELDEIRY, WS;TOKINO, T;VOGELSTEIN, B
p53激活特定序列转录的能力表明，p53诱导的基因可能介导其作为肿瘤抑制因子的生物学作用。使用消减杂交方法，我们确定了一个基因，命名为WAF 1，其诱导与野生型，但不是突变型p53基因在人脑肿瘤细胞系中的表达。WAF 1基因定位于染色体6p21.2，其序列、结构和p53激活在啮齿类动物中是保守的。 WAF1 cDNA的引入抑制了培养中的人脑、肺和结肠肿瘤细胞的生长。使用酵母增强子陷阱，p53结合位点被确定为WAF 1编码序列上游2.4 kb。WAF 1启动子，包括这个p53结合位点，赋予p53依赖性诱导后，异源报告基因。这些研究定义了一个基因，其表达直接由p53诱导，并且可能是p53依赖性肿瘤生长抑制的重要介质。
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.