Functional similarity between adenovirus e1b 19k gene and bcl2 oncogene - mutant complementation and suppression of cell-death induced by DNA-damaging agents.
Functional similarity between adenovirus e1b 19k gene and bcl2 oncogene - mutant complementation and suppression of cell-death induced by DNA-damaging agents.
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DOI：
10.3892/ijo.3.3.467
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发表时间：
1993-09
影响因子：
5.2
通讯作者：
B. Taródi;T. Subramanian;G. Chinnadurai
中科院分区：
文献类型：
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作者：
B. Taródi;T. Subramanian;G. Chinnadurai
腺病毒突变体在由早期区域E1B编码的19 kD蛋白（19 K基因）中有缺陷，以类似于在由许多化学、物理和生物刺激诱导的程序性细胞死亡（凋亡）期间观察到的核小体间DNA片段化的方式诱导DNA片段化。Zn++离子有效地抑制了19K突变体诱导的DNA片段化，这与它们在细胞凋亡过程中抑制DNA片段化一致。由于细胞原癌基因Bcl 2已被证明可以抑制DNA片段化和由此产生的程序性细胞死亡，我们进行了功能互补分析，以确定E1B 19 kD蛋白是否在功能上类似于Bcl 2蛋白。我们的结果表明，19K突变体诱导的DNA断裂可以有效地抑制稳定表达的人Bcl 2蛋白。此外，19 kD和Bcl 2蛋白也具有类似的功能，以抑制DNA损伤剂顺铂和UV诱导的DNA片段化和细胞死亡。
Adenovirus mutants defective in a 19 kD protein (19K gene) encoded by the early region E1B induce DNA fragmentation in a manner similar to the internucleosomal DNA fragmentation observed during programmed cell death (apoptosis) induced by a number of chemical, physical and biological stimuli. Zn++ ions effectively suppressed DNA fragmentation induced by a 19K mutant consistent with their inhibition of DNA fragmentation during apoptosis. Since the cellular proto-oncogene Bcl2 has been shown to suppress DNA fragmentation and the resulting programmed cell death, we have carried out a functional complementation analysis to determine whether the E1B 19 kD protein is functionally similar to the Bcl2 protein. Our results indicate that the DNA fragmentation induced by the 19K mutant can be efficiently suppressed by stable expression of human Bcl2 protein. Further, the 19 kD and Bcl2 proteins also function similarly to suppress DNA fragmentation and cell death induced by the DNA damaging agents cisplatin and UV.