IDENTIFICATION OF A HUMAN UBIQUITIN-CONJUGATING ENZYME THAT MEDIATES THE E6-AP-DEPENDENT UBIQUITINATION OF P53
IDENTIFICATION OF A HUMAN UBIQUITIN-CONJUGATING ENZYME THAT MEDIATES THE E6-AP-DEPENDENT UBIQUITINATION OF P53
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DOI：
10.1073/pnas.91.19.8797
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发表时间：
1994-09-13
影响因子：
11.1
通讯作者：
HOWLEY, PM
中科院分区：
文献类型：
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作者：
SCHEFFNER, M;HUIBREGTSE, JM;HOWLEY, PM
致瘤性人乳头瘤病毒16型和18型的E6蛋白通过泛素依赖性蛋白水解途径促进肿瘤抑制蛋白p53的快速降解。E6蛋白与100 kDa的细胞蛋白E6- ap结合。E6和E6- ap复合物特异性地与p53相互作用并诱导p53的泛素化，该反应需要泛素活化酶（E1）和含有哺乳动物泛素结合酶（E2）的细胞片段，这种哺乳动物E2活性可以由拟南芥细菌表达的UBC8取代，该UBC8属于E2s亚家族，包括酵母UBC4和UBC5，在氨基酸水平上高度保守。在本文中，我们描述了克隆人类cDNA编码人类E2，我们命名为UbcH5，这与拟南芥UBC8和该亚家族的其他成员有关。我们证明UbcH5可以在E6/E6- ap诱导的p53泛素化中发挥作用。
The E6 protein of the oncogenic human papillomavirus types 16 and 18 facilitates the rapid degradation of the tumor-suppressor protein p53 via the ubiquitin dependent proteolytic pathway. The E6 protein binds to a cellular protein of 100 kDa termed E6-AP. The complex of E6 and E6-AP specifically interacts with p53 and induces the ubiquitination of p53 in a reaction which requires the ubiquitin-activating enzyme (E1) and a cellular fraction thought to contain a mammalian ubiquitin-conjugating enzyme (E2), This mammalian E2 activity could be replaced with bacterially expressed UBC8 from Arabidopsis thaliana, which belongs to a subfamily of E2s including yeast UBC4 and UBC5 which are highly conserved at the amino acid level. In this paper we describe the cloning of a human cDNA encoding a human E2 that we have designated UbcH5 and that is related to Arabidopsis UBC8 and the other members of this subfamily. We demonstrate that UbcH5 can function in the E6/E6-AP-induced ubiquitination of p53.