Fields S, Jang S K
Department of Microbiology, School of Medicine, State University of New York, Stony Brook 11794.
Science. 1990 Aug 31;249(4972):1046-9. doi: 10.1126/science.2144363.
The p53 gene is frequently mutated in a wide variety of human cancers. However, the role of the wild-type p53 gene in growth control is not known. Hybrid proteins that contain the DNA binding domain of yeast GAL4 and portions of p53 have been used to show that the p53 protein contains a transcription-activating sequence that functions in both yeast and mammalian cells. The NH2-terminal 73 residues of p53 activated transcription in mammalian cells as efficiently as the herpes virus protein VP16, which contains one of the strongest known activation domains. Combined with previous data that showed p53 is localized to the nucleus and can bind to DNA, these results support the idea that one function of p53 is to activate the transcription of genes that suppress cell proliferation.
p53基因在多种人类癌症中经常发生突变。然而,野生型p53基因在生长控制中的作用尚不清楚。含有酵母GAL4的DNA结合结构域和部分p53的杂交蛋白已被用于表明p53蛋白含有一个在酵母和哺乳动物细胞中均起作用的转录激活序列。p53的NH2末端73个残基在哺乳动物细胞中激活转录的效率与疱疹病毒蛋白VP16相同,VP16含有已知最强的激活结构域之一。结合先前显示p53定位于细胞核并能与DNA结合的数据,这些结果支持了p53的一个功能是激活抑制细胞增殖的基因转录的观点。