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腺病毒E1A蛋白介导细胞转化的靶点

Cellular targets for transformation by the adenovirus E1A proteins.

作者信息

Whyte P, Williamson N M, Harlow E

机构信息

Cold Spring Harbor Laboratory, New York 11724.

出版信息

Cell. 1989 Jan 13;56(1):67-75. doi: 10.1016/0092-8674(89)90984-7.

Abstract

Three cellular proteins, including species of 300,000 daltons and 107,000 daltons as well as p105-RB, the product of the retinoblastoma susceptibility gene, stably interact with the adenovirus E1A proteins. To help determine the functional basis of these interactions, the regions of E1A that participate in these interactions were mapped using a series of deletion mutants. The 300,000 dalton and the 107,000 dalton proteins interacted with sequences within amino acids 1 to 76 and 121 to 127, respectively. Interaction with the third cellular protein, p105-RB, required the presence of sequences from two noncontiguous regions of the E1A polypeptide chain, amino acids 30 to 60 and 121 to 127. The regions of E1A that are required for these interactions coincided precisely with the regions of E1A that are required for its transforming function. These results suggest that the interactions with these cellular proteins are fundamental to the transforming activity of E1A.

摘要

三种细胞蛋白,包括分子量为300,000道尔顿和107,000道尔顿的蛋白以及视网膜母细胞瘤易感基因的产物p105-RB,能与腺病毒E1A蛋白稳定相互作用。为了帮助确定这些相互作用的功能基础,利用一系列缺失突变体对参与这些相互作用的E1A区域进行了定位。分子量为300,000道尔顿的蛋白和分子量为107,000道尔顿的蛋白分别与氨基酸1至76和121至127内的序列相互作用。与第三种细胞蛋白p105-RB相互作用需要E1A多肽链两个不连续区域的序列存在,即氨基酸30至60和121至127区域。这些相互作用所需的E1A区域与E1A转化功能所需的区域精确重合。这些结果表明,与这些细胞蛋白的相互作用是E1A转化活性的基础。

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