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腺病毒E1B 19K基因与bcl2癌基因之间的功能相似性——DNA损伤剂诱导的细胞死亡的突变互补与抑制

Functional similarity between adenovirus e1b 19k gene and bcl2 oncogene - mutant complementation and suppression of cell-death induced by DNA-damaging agents.

作者信息

Tarodi B, Subramanian T, Chinnadurai G

机构信息

ST LOUIS UNIV,MED CTR,INST MOLEC VIROL,3681 PK AVE,ST LOUIS,MO 63110.

出版信息

Int J Oncol. 1993 Sep;3(3):467-72. doi: 10.3892/ijo.3.3.467.

DOI:10.3892/ijo.3.3.467
PMID:21573386
Abstract

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.

摘要

腺病毒早期区域E1B编码的一种19kD蛋白(19K基因)存在缺陷的腺病毒突变体,以类似于在多种化学、物理和生物刺激诱导的程序性细胞死亡(凋亡)过程中观察到的核小体间DNA片段化的方式诱导DNA片段化。锌离子有效地抑制了19K突变体诱导的DNA片段化,这与其对凋亡过程中DNA片段化的抑制作用一致。由于细胞原癌基因Bcl2已被证明可抑制DNA片段化及由此导致的程序性细胞死亡,我们进行了功能互补分析,以确定E1B 19kD蛋白在功能上是否与Bcl2蛋白相似。我们的结果表明,人Bcl2蛋白的稳定表达可有效抑制19K突变体诱导的DNA片段化。此外,19kD蛋白和Bcl2蛋白在抑制顺铂和紫外线等DNA损伤剂诱导的DNA片段化和细胞死亡方面也具有相似的功能。

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