Narisawa-Saito Mako, Kiyono Tohru
Virology Division, National Cancer Center Research Institute, Tokyo.
Nihon Rinsho. 2009 Jan;67(1):53-61.
Human papillomaviruses (HPVs) are believed to be the primary causal agents for development of pre-neoplastic and malignant lesions of the uterine cervix and high-risk types such as type 16 and 18 are associated with more than 90% of all cervical carcinomas. The E6 and E7 genes of HPVs are thought to play causative roles, since E6 promotes the degradation of p53 through its interaction with E6AP, an E3 ubiquitin ligase, whereas E7 binds to the retinoblastoma protein pRb and disrupts its complex formation with E2F transcription factors. Although prophylactic vaccines have become available, it is still necessary to clarify the mechanisms of HPV-induced carcinogenesis because of the widespread nature of HPV infection. In this article, the mechanisms of high-risk HPV E6 and E7-induced multistep carcinogenesis and recently identified functions of these oncoproteins are reviewed.
人乳头瘤病毒（HPV）被认为是子宫颈癌前病变和恶性病变发展的主要致病因子，16型和18型等高风险型别与90%以上的宫颈癌相关。HPV的E6和E7基因被认为起着致病作用，因为E6通过与E3泛素连接酶E6AP相互作用促进p53降解，而E7与视网膜母细胞瘤蛋白pRb结合并破坏其与E2F转录因子的复合物形成。尽管预防性疫苗已经问世，但由于HPV感染的广泛性，仍有必要阐明HPV诱导致癌的机制。本文综述了高危型HPV E6和E7诱导多步骤致癌的机制以及这些癌蛋白最近发现的功能。
