THE HUMAN PAPILLOMA VIRUS-16 E7-ONCOPROTEIN IS ABLE TO BIND TO THE RETINOBLASTOMA GENE-PRODUCT

THE HUMAN PAPILLOMA VIRUS-16 E7-ONCOPROTEIN IS ABLE TO BIND TO THE RETINOBLASTOMA GENE-PRODUCT
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DOI:
10.1126/science.2537532
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发表时间:
1989-02-17
期刊:
影响因子:
56.9
通讯作者:
HARLOW, E
HARLOW, E
中科院分区:
综合性期刊1区
文献类型:
--
作者:
DYSON, N;HOWLEY, PM;HARLOW, E

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视网膜母细胞瘤基因RB 1的缺失或突变是许多肿瘤和肿瘤细胞系的共同特征。最近,RB 1基因产物p105-RB已显示与两种DNA肿瘤病毒的癌蛋白,腺病毒E1 A蛋白和猿猴病毒40(SV 40)大T抗原形成稳定的蛋白/蛋白复合物。这两种病毒都不被认为与人类癌症有关,但它们可以在啮齿动物中引起肿瘤。RB抑癌蛋白与腺病毒或SV 40癌蛋白之间的结合可以用免疫共沉淀混合试验在体外重现。这些试验已被用于证明,人乳头瘤病毒16型的E7癌蛋白可以与p105-RB形成类似的复合物。人类乳头状瘤病毒16被发现与大约50%的宫颈癌有关。这些结果表明,这三种DNA病毒可能利用类似的机制转化和牵连RB结合作为一个可能的步骤,在人乳头瘤病毒相关的致癌作用。
Deletions or mutations of the retinoblastoma gene, RB1, are common features of many tumors and tumor cell lines. Recently, the RB1 gene product, p105-RB, has been shown to form stable protein/protein complexes with the oncoproteins of two DNA tumor viruses, the adenovirus E1A proteins and the simian virus 40 (SV40) large T antigen. Neither of these viruses is thought to be associated with human cancer, but they can cause tumors in rodents. Binding between the RB anti-oncoprotein and the adenovirus or SV40 oncoprotein can be recapitulated in vitro with coimmunoprecipitation mixing assays. These assays have been used to demonstrate that the E7 oncoprotein of the human papilloma virus type-16 can form similar complexes with p105-RB. Human papilloma virus-16 is found associated with approximately 50 percent of cervical carcinomas. These results suggest that these three DNA viruses may utilize similar mechanisms in transformation and implicate RB binding as a possible step in human papilloma virus-associated carcinogenesis.