The oncogenic role of human papillomavirus proteins.
The oncogenic role of human papillomavirus proteins.
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人乳头瘤病毒蛋白的致癌作用。
DOI：
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发表时间：
1996
影响因子：
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通讯作者：
M. Barbosa
中科院分区：
文献类型：
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作者：
M. Barbosa
每种人乳头瘤病毒 (HPV) 类型都具有不同的基因型，并感染独特解剖部位的上皮细胞。在所描述的 HPV 类型中，有一个亚型与生殖器疾病相关，其中的一个亚型存在于 90% 的生殖器癌症中。尽管在良性感染中，病毒基因组以附加体的形式存在，但在癌症中，它是整合的。整合事件总是导致两种病毒蛋白 E6 和 E7 的表达。这两种蛋白质能够单独转化细胞并协同使原代人类上皮细胞永生化。分子分析表明，癌症中普遍存在的“高危”型 HPV 编码的 E6 蛋白与 p53 肿瘤抑制蛋白和一种称为 E6-AP 的细胞蛋白形成三联复合物，导致 p53 降解。 “高危”HPV 类型编码的 E7 蛋白与视网膜母细胞瘤肿瘤抑制因子 pRb 具有高亲和力相关性。 E7 蛋白还与已知在细胞周期调节中发挥作用的其他细胞因子相关。这篇综述讨论了体外和体内的分子和生物学证据，支持“高危”HPV 型编码的 E6 和 E7 蛋白在宫颈癌发生中的直接作用。
Each human papillomavirus (HPV) type is genotypically distinct and infects epithelial cells at unique anatomic sites. Among the HPV types described, a subgroup is associated with genital disease and a subset of these is found in 90% of genital cancers. Although in benign infections the viral genome is present as an episome, in cancers it is integrated. The integration event invariably results in the expression of two viral proteins, E6 and E7. These two proteins are capable of transforming cells individually and cooperate to immortalize primary human epithelial cells. Molecular analysis has revealed that the E6 protein encoded by the HPV "high risk" types prevalent in cancers forms a tripartite complex with the p53 tumor suppressor protein and a cellular protein termed E6-AP, resulting in the degradation of p53. The E7 protein encoded by "high-risk" HPV types shows high-affinity association with the retinoblastoma tumor suppressor, pRb. The E7 protein associates also with other cellular factors known to play a role in cell cycle regulation. This review discusses the evidence, molecular and biological, in vitro and in vivo, supporting a direct role for the "high-risk" HPV type encoded E6 and E7 proteins in cervical carcinogenesis.