THE HPV-16 E6 AND E6-AP COMPLEX FUNCTIONS AS A UBIQUITIN-PROTEIN LIGASE IN THE UBIQUITINATION OF P53
THE HPV-16 E6 AND E6-AP COMPLEX FUNCTIONS AS A UBIQUITIN-PROTEIN LIGASE IN THE UBIQUITINATION OF P53
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DOI：
10.1016/0092-8674(93)90384-3
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发表时间：
1993-11-05
期刊：
影响因子：
64.5
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
泛素依赖的蛋白水解途径在选择性蛋白质降解中起主要作用。蛋白质的泛素化需要泛素活化酶（E1）、泛素缀合酶（E2）和在某些情况下的泛素-蛋白质连接酶（E3）的顺序作用。致癌的人乳头瘤病毒（HPV）16型和18型利用这种细胞蛋白水解系统靶向肿瘤抑制蛋白p53。HPV E6癌蛋白与100 kd的细胞蛋白结合，称为E6相关蛋白（E6-AP）。E6-E6-AP复合物特异性地与p53相互作用，导致p53的快速泛素依赖性降解。在这里，我们报告的E6-E6-AP介导的p53泛素化的必要因素的纯化和鉴定。在哺乳动物细胞中，p53的泛素化需要E1酶和新的E2，而E3活性由E6-E6-AP复合物赋予。此外，E6-AP似乎在E6不存在的情况下具有泛素-蛋白连接酶活性。
The ubiquitin-dependent proteolytic pathway plays a major role in selective protein degradation. Ubiquitination of proteins requires the sequential action of the ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzymes (E2), and in some cases ubiquitin-protein ligases (E3s). The oncogenic human papillomavirus (HPV) types 16 and 18 utilize this cellular proteolytic system to target the tumor suppressor protein p53. The HPV E6 oncoprotein binds to a cellular protein of 100 kd, termed E6-associated protein (E6-AP). The E6-E6-AP complex specifically interacts with p53, resulting in the rapid ubiquitin-dependent degradation of p53. Here we report the purification and identification of the factors necessary for the E6-E6-AP-mediated ubiquitination of p53. The ubiquitination of p53 requires the E1 enzyme and a novel E2 in mammalian cells, while E3 activity is conferred by the E6-E6-AP complex. Furthermore, E6-AP appears to have ubiquitin-protein ligase activity in the absence of E6.