REGULATION OF APOPTOSIS BY VIRAL TRANSFORMING PROTEINS

腺病毒编码参与转化的两个基因，E1 A和E1 B， E1 A基因的产物 刺激细胞增殖，但不能单独转化细胞， 诱导程序性细胞死亡（凋亡）。 E1 B的表达 基因或人bcl-2原癌基因，阻断E1 A诱导的细胞死亡， 高效生产转化。E1 B基因编码两个 产生独特的19 K和55 K蛋白。 这两 蛋白质通过阻断诱导的细胞死亡来增强E1 A的转化。 另外，E1 B19 K蛋白可阻断肿瘤诱导的细胞凋亡 坏死因子-α（TNF-α）和抗Fas抗体。 的最新结果 白色博士的实验室已经表明，E1 A蛋白诱导p53， turn诱导细胞凋亡。 E1 B 55 K蛋白直接结合p53， 可能会像SV 40 T抗原一样干扰其功能。 的 E1 B19 K蛋白在抑制p53中的作用机制是 未知这项建议的目的是确定机制， 通过p53调节细胞凋亡。 该方法是定义E1 A，c-myc， TNF-α和抗Fas抗体诱导p53和细胞凋亡以及E1 B是如何诱导细胞凋亡的。 19 K和bcl-2蛋白阻断这种作用。

Adenovirus encodes two genes involved in transformation, E1A and E1B, which cooperate to transform primary rodent cells.The E1A gene products stimulate cell proliferation but fail to transform cells alone due to the induction of programmed cell death (apoptosis). Expression of the E1B gene or the human bcl-2 proto-oncogene, blocks E1A-induced cell death to produce transformation with high efficiency. The E1B gene encodes two products the l9K and 55K proteins that are unique proteins. Both of these proteins enhance transformation by E1A by blocking induced cell death. Additionally, the E1B 19K protein can block apoptosis induced by tumor necrosis factor-a (TNF-a) and anti-Fas antibodies. Recent results from Dr. White's laboratory has shown that the E1A proteins induce p53 which in turn induces apoptosis. The E1B 55K protein directly binds p53 and presumably interferes with it's function like SV40 T antigen. The mechanism of action of the E1B l9K protein in suppression of p53 is unknown. The aim of this proposal is to ascertain the mechanism by which apoptosis by p53 is regulated. The approach is to define how E1A, c-myc, TNF-a, and anti-Fas antibodies induce p53 and apoptosis and how the E1B l9K and bcl-2 proteins block this effect.