Dyson N, Howley P M, Münger K, Harlow E
Cold Spring Harbor Laboratory, NY 11724.
Science. 1989 Feb 17;243(4893):934-7. doi: 10.1126/science.2537532.
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.
视网膜母细胞瘤基因RB1的缺失或突变是许多肿瘤及肿瘤细胞系的常见特征。最近研究表明，RB1基因产物p105-RB能与两种DNA肿瘤病毒的癌蛋白形成稳定的蛋白质/蛋白质复合物，这两种病毒分别是腺病毒E1A蛋白和猿猴病毒40（SV40）大T抗原。虽然这两种病毒都不被认为与人类癌症相关，但它们可在啮齿动物中引发肿瘤。RB抑癌蛋白与腺病毒或SV40癌蛋白之间的结合可通过体外免疫共沉淀混合试验重现。这些试验已被用于证明人乳头瘤病毒16型的E7癌蛋白能与p105-RB形成类似的复合物。约50%的宫颈癌中可发现人乳头瘤病毒16型。这些结果表明，这三种DNA病毒在转化过程中可能利用相似机制，并且提示RB结合可能是人乳头瘤病毒相关致癌作用中的一个步骤。
