Debbas M, White E
Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey 08854.
Genes Dev. 1993 Apr;7(4):546-54. doi: 10.1101/gad.7.4.546.
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 E1A. E1B 19K and 55K proteins provide separate mechanisms that disable the cell suicide pathway of p53.
腺病毒E1A和E1B癌基因对原代啮齿动物细胞的转化是一个两步过程，其中E1A依赖的增殖诱导与E1B依赖的程序性细胞死亡（凋亡）抑制相偶联。E1B基因编码两种不同的转化蛋白，即19K和55K蛋白，它们都能独立地与E1A协同作用。E1B 19K或55K蛋白，或人类Bcl-2蛋白，具有抑制凋亡的功能，从而允许与E1A一起进行转化。E1B 55K蛋白可阻断p53肿瘤抑制蛋白的功能，这表明p53可能介导E1A诱导的凋亡。在突变构象中，p53阻断了E1A诱导的凋亡，并有效地与E1A协同作用以转化原代细胞。当p53恢复到野生型构象时，E1A + p53转化体通过凋亡发生细胞死亡。p53从突变型向野生型构象转变所诱导的这种凋亡受到E1B 19K蛋白表达的抑制。因此，p53蛋白可能通过启动对E1A导致的生长调控失调的细胞自杀反应而发挥肿瘤抑制作用。E1B 19K和55K蛋白提供了不同的机制来使p53的细胞自杀途径失活。
