DEFINITION OF ADENOVIRUS TYPE-5 FUNCTIONS INVOLVED IN THE INDUCTION OF CHROMOSOMAL-ABERRATIONS IN HUMAN-CELLS

DEFINITION OF ADENOVIRUS TYPE-5 FUNCTIONS INVOLVED IN THE INDUCTION OF CHROMOSOMAL-ABERRATIONS IN HUMAN-CELLS
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DOI:
10.1099/0022-1317-71-4-801
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发表时间:
1990-04-01
影响因子:
3.8
通讯作者:
BACCHETTI, S
BACCHETTI, S
中科院分区:
医学3区
文献类型:
--
作者:
CAPOROSSI, D;BACCHETTI, S

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5 型腺病毒 (Ad5) 感染人胚胎肾细胞会诱导细胞染色体畸变(间隙和断裂)。我们进行了一项研究,利用大量 Ad5 突变体来鉴定导致细胞遗传学损伤发生的病毒功能。我们的研究结果表明,Ad5 早期区域 1A (E1A) 基因产物的表达对于诱导染色体畸变是必要的,而其他早期病毒基因产物似乎不会促成这种表型。我们还表明,主要的 E1A 基因产物(243 个氨基酸和 289 个氨基酸的蛋白质)的表达是在野生型水平诱导损伤所必需的,尽管 289 个氨基酸的蛋白质似乎保留了其自身可检测的活性。最后,我们观察到,E1A 蛋白氨基末端区域和 289 个氨基酸蛋白反式激活结构域的缺失可以防止细胞遗传学损伤的发生,而蛋白质其他位置的突变不会影响这一过程。
Infection of human embryonic kidney cells with adenovirus type 5 (Ad5) induces aberrations (gaps and breaks) in the cell chromosomes. We have conducted a study utilizing a large number of Ad5 mutants to identify the viral functions that are responsible for the occurrence of cytogenetic damage. The results of our investigation have indicated that expression of the gene products of the Ad5 early region 1A (E1A) is necessary for the induction of chromosomal aberrations and that other early viral gene products do not appear to contribute to this phenotype. We have also shown that expression of both the major E1A gene products, the 243 amino acid and the 289 amino acid proteins, is required for induction of damage at wild-type levels, although the 289 amino acid protein appears to retain detectable activity on its own. Lastly, we have observed that deletions in the amino-terminal region of the E1A proteins and in the transactivating domain of the 289 amino acid protein prevent the occurrence of cytogenetic damage, whereas mutations elsewhere in the proteins do not affect this process.