LOCALIZATION OF THE E6-AP REGIONS THAT DIRECT HUMAN PAPILLOMAVIRUS E6 BINDING, ASSOCIATION WITH P53, AND UBIQUITINATION OF ASSOCIATED PROTEINS
LOCALIZATION OF THE E6-AP REGIONS THAT DIRECT HUMAN PAPILLOMAVIRUS E6 BINDING, ASSOCIATION WITH P53, AND UBIQUITINATION OF ASSOCIATED PROTEINS
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DOI：
10.1128/mcb.13.8.4918
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发表时间：
1993-08-01
影响因子：
5.3
通讯作者：
HOWLEY, PM
中科院分区：
文献类型：
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作者：
HUIBREGTSE, JM;SCHEFFNER, M;HOWLEY, PM
E6- ap是一种100 kda的细胞蛋白，介导人乳头瘤病毒16型和18型E6蛋白与p53的相互作用。p53与E6和E6- ap的关联促进了p53的特异性泛素化和随后的体外蛋白水解降解。我们最近分离了一个编码E6- ap的cDNA，并绘制了E6- ap与E6结合、与p53关联以及p53泛素化的功能域。E6结合域由分子中心部分的18个氨基酸区域组成。从E6- ap中删除这18个氨基酸会导致E6和p53结合活性的丧失。指导p53结合的区域横跨E6结合域，由大约500个氨基酸组成。E6- ap序列除了与E6和p53形成稳定三元配合物所需的序列外，也是刺激p53泛素化所必需的。这些序列位于E6-AP的c端84个氨基酸内。E6依赖性p53泛素化所需要的整个区域也是人工E6融合蛋白泛素化所需要的。
E6-AP is a 100-kDa cellular protein that mediates the interaction of the human papillomavirus type 16 and 18 E6 proteins with p53. The association of p53 with E6 and E6-AP promotes the specific ubiquitination and subsequent proteolytic degradation of p53 in vitro. We recently isolated a cDNA encoding E6-AP and have now mapped functional domains of E6-AP involved in binding E6, association with p53, and ubiquitination of p53. The E6 binding domain consists of an 18-amino-acid region within the central portion of the molecule. Deletion of these 18 amino acids from E6-AP results in loss of both E6 and p53 binding activities. The region that directs p53 binding spans the E6 binding domain and consists of approximately 500 amino acids. E6-AP sequences in addition to those required for formation of a stable ternary complex with E6 and p53 are necessary to stimulate the ubiquitination of p53. These sequences lie within the C-terminal 84 amino acids of E6-AP. The entire region required for E6-dependent ubiquitination of p53 is also required for the ubiquitination of an artificial E6 fusion protein.