The regions of the retinoblastoma protein needed for binding to adenovirus E1A or SV40 large T antigen are common sites for mutations.

The regions of the retinoblastoma protein needed for binding to adenovirus E1A or SV40 large T antigen are common sites for mutations.
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DOI:
10.1002/j.1460-2075.1990.tb08221.x
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发表时间:
1990-04
期刊:
The EMBO Journal
影响因子:
--
通讯作者:
Qianjin Hu;N. Dyson;E. Harlow
Qianjin Hu;N. Dyson;E. Harlow
中科院分区:
其他
文献类型:
--
作者:
Qianjin Hu;N. Dyson;E. Harlow

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视网膜母细胞瘤(RB)基因的蛋白产物被认为在限制细胞增殖的途径中起作用。最近,来自三种不同类型的DNA肿瘤病毒的转化蛋白已被证明与RB蛋白形成复合物。遗传学研究表明,这些与RB蛋白的相互作用是这些病毒转化的重要步骤。为了更好地理解RB-病毒癌蛋白复合物的功能,我们绘制了这些关联所必需的RB蛋白区域。发现RB的两个非连续区域对于与腺病毒E1 A或SV 40大T抗原形成复合物是必需的。这两个区域存在于氨基酸393和572以及646和772之间。有趣的是,RB上的这些结合位点与RB基因的天然存在的失活突变的位置重叠。这些结果有力地表明,这些病毒癌蛋白靶向的蛋白质结构域是RB蛋白正常功能中的重要位点。
The protein product of the retinoblastoma (RB) gene is thought to function in a pathway that restricts cell proliferation. Recently, transforming proteins from three different classes of DNA tumor viruses have been shown to form complexes with the RB protein. Genetic studies suggest that these interactions with the RB protein are important steps in transformation by these viruses. In order to understand better the function of the RB‐viral oncoprotein complexes, we have mapped the regions of the RB protein that are necessary for these associations. Two non‐contiguous regions of RB were found to be essential for complex formation with adenovirus E1A or SV40 large T antigen. These two regions are found between amino acids 393 and 572 and 646 and 772. Interestingly, these binding sites on RB overlap with the positions of naturally occurring, inactivating mutations of the RB gene. These results strongly suggest that these viral oncoproteins are targeting a protein domain that is an important site in the normal function of the RB protein.