Huibregtse J M, Beaudenon S L
Department of Molecular Biology and BIochemistry, Rutgers University, Piscataway, NJ 08855, USA.
Semin Cancer Biol. 1996 Dec;7(6):317-26. doi: 10.1006/scbi.1996.0041.
The E6 protein is a major transforming protein of many types of papillomaviruses. Mechanistically, the best characterized E6 proteins are those of the high-risk genital HPVs (e.g. HPV-16 and 18 E6), which function, at least in part, by inactivating the p53 tumor suppressor protein. Biochemical studies have shown that this occurs by targeted degradation of p53, dependent on the E6-AP ubiquitin-protein ligase. The model that has emerged from E6/E6-AP-dependent p53 degradation has provided insight into both HPV-associated carcinogenesis and the problem of substrate specificity of the ubiquitin system. Several observations suggest that the high-risk HPV E6 proteins may also have activities in addition to inactivation of p53.
E6蛋白是多种乳头瘤病毒的主要转化蛋白。从机制上讲，特征最明确的E6蛋白是高危型生殖器人乳头瘤病毒（如HPV - 16和18 E6）的E6蛋白，其功能至少部分是通过使p53肿瘤抑制蛋白失活来实现的。生化研究表明，这是通过依赖E6 - AP泛素 - 蛋白连接酶对p53进行靶向降解而发生的。从E6 / E6 - AP依赖的p53降解中得出的模型，为HPV相关的致癌作用以及泛素系统的底物特异性问题提供了见解。一些观察结果表明，高危型HPV E6蛋白除了使p53失活外，可能还具有其他活性。
