WILD-TYPE P53 MEDIATES APOPTOSIS BY E1A, WHICH IS INHIBITED BY E1B
WILD-TYPE P53 MEDIATES APOPTOSIS BY E1A, WHICH IS INHIBITED BY E1B
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DOI：
10.1101/gad.7.4.546
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发表时间：
1993-04-01
影响因子：
10.5
通讯作者：
WHITE, E
中科院分区：
文献类型：
--
作者：
DEBBAS, M;WHITE, E
腺病毒E1 A和E1 B癌基因对原代啮齿动物细胞的转化是一个两步过程，其中E1 A依赖性增殖诱导与E1 B依赖性程序性细胞死亡（凋亡）抑制偶联。E1 B基因编码两种不同的转化蛋白，19 K和55 K蛋白，这两种蛋白都独立地与E1 A合作。E1 B 19 K或55 K蛋白或人Bcl-2蛋白的功能是抑制细胞凋亡，从而允许用E1 A转化。E1 B 55 K蛋白阻断p53肿瘤抑制蛋白的功能，表明p53可能通过E1 A介导细胞凋亡。在突变体构象中，p53阻断了E1 A诱导的凋亡，并有效地与E1 A合作转化原代细胞。当p53恢复到野生型构象时，E1 A +p53转化体通过凋亡进行细胞死亡。E1 B 19 K蛋白的表达抑制了p53从突变体到野生型形式的构象转变对细胞凋亡的诱导。因此，p53蛋白可能通过启动细胞自杀反应以解除EIA对生长控制的调节而起到肿瘤抑制剂的作用。E1 B 19 K和55 K蛋白提供了使p53的细胞自杀途径失效的单独机制。
Transformation of primary rodent cells by the adenovirus E1A and E1B oncogenes is a two-step process, where E1A-dependent induction of proliferation is coupled to E1B-dependent suppression of programmed cell death (apoptosis). The E1B gene encodes two distinct transforming proteins, the 19K and 55K proteins, both of which independently cooperate with E1A. E1B 19K or 55K protein, or the human Bcl-2 protein, functions to suppress apoptosis and thereby permits transformation with E1A. The E1B 55K protein blocks p53 tumor suppressor protein function, indicating that p53 may mediate apoptosis by E1A. In the mutant conformation, p53 blocked induction of apoptosis by E1A and efficiently cooperated with E1A to transform primary cells. When p53 was returned to the wild-type conformation, E1A+p53 transformants underwent cell death by apoptosis. This induction of apoptosis by conformational shift of p53 from the mutant to the wild-type form was inhibited by expression of the E1B 19K protein. Thus, the p53 protein may function as a tumor suppressor by initiating a cell suicide response to deregulation of growth control by EIA. E1B 19K and 55K proteins provide separate mechanisms that disable the cell suicide pathway of p53.