HEPATITIS-B VIRUS X-PROTEIN INTERACTS WITH A PROBABLE CELLULAR DNA-REPAIR PROTEIN

HEPATITIS-B VIRUS X-PROTEIN INTERACTS WITH A PROBABLE CELLULAR DNA-REPAIR PROTEIN
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DOI:
10.1128/jvi.69.2.1107-1114.1995
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发表时间:
1995-02-01
影响因子:
5.4
通讯作者:
BUTEL, JS
BUTEL, JS
中科院分区:
医学2区
文献类型:
--
作者:
LEE, TH;ELLEDGE, SJ;BUTEL, JS

文献摘要

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乙型肝炎病毒(HBV) X蛋白在转录反激活和肿瘤发生中的作用机制尚不清楚,我们使用酵母双杂交系统鉴定了一种可以与HBV X蛋白相互作用的细胞蛋白。该蛋白被命名为x相关蛋白1 (XAP-1),是从猴细胞cDNA文库中发现的紫外线损伤dna结合蛋白(UV-DDB)的人类同源物。UV-DDB被认为参与DNA修复。通过对表达这两种蛋白的酵母细胞裂解物进行免疫沉淀,以及在HeLa细胞提取物中或通过体外翻译合成谷胱甘肽s -转移酶融合蛋白和XAP-1蛋白的X蛋白进行体外混合,验证了X蛋白和XAP-1蛋白之间的相互作用。我们推测X蛋白与DNA修复蛋白的相互作用可能会招募细胞蛋白来修复部分双链HBV基因组,或者可能会改变细胞转录过程。对细胞DNA修复系统的影响可能解释了HBV在肝癌发展中的辅助因子作用。
The mechanism of action of hepatitis B virus (HBV) X protein in transcriptional transactivation and in tumorigenesis remains obscure, We have used the yeast two-hybrid system to identify a cellular protein that can interact with HBV X protein. This protein, designated X-associated protein 1 (XAP-1), is a human homolog of the UV-damaged DNA-binding protein (UV-DDB) recovered from a monkey cell cDNA library. UV-DDB is presumed to be involved in DNA repair. The interaction between X protein and XAP-1 protein was verified by immunoprecipitation of yeast cell lysates expressing both proteins and by in vitro mixing with X protein expressed as a glutathione S-transferase fusion protein and XAP-1 protein either in HeLa cell extracts or synthesized by in vitro translation. We speculate that the interaction of X protein with a DNA repair protein may recruit cellular proteins to repair the partially double-stranded HBV genome or may modify cellular transcription processes. An effect on the cellular DNA repair system may explain a cofactor role for HBV in liver cancer development.