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首页> 外文期刊>Molecular and Cellular Biology >Localization of the E6-AP regions that direct human papillomavirus E6 binding, association with p53, and ubiquitination of associated proteins.
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Localization of the E6-AP regions that direct human papillomavirus E6 binding, association with p53, and ubiquitination of associated proteins.

机译：指导人类乳头瘤病毒E6结合，与p53结合以及相关蛋白的泛素化的E6-AP区的定位。

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摘要

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.
机译：E6-AP是一种100 kDa的细胞蛋白，可介导16型和18型人乳头瘤病毒E6蛋白与p53的相互作用。 p53与E6和E6-AP的结合促进了p53的特异性泛素化和随后的蛋白水解降解。我们最近分离了一个编码E6-AP的cDNA，现在已经绘制了E6-AP的功能域，该域涉及结合E6，与p53的结合以及p53的泛素化。 E6结合结构域由分子中心部分内的18个氨基酸区域组成。从E6-AP中删除这18个氨基酸导致E6和p53结合活性的丧失。指导p53结合的区域跨越E6结合域，由大约500个氨基酸组成。除了与E6和p53形成稳定的三元复合物所需的序列外，E6-AP序列对于刺激p53的泛素化也是必需的。这些序列位于E6-AP的C末端84个氨基酸内。人工E6融合蛋白的泛素化还需要p53的E6依赖性泛素化所需的整个区域。

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