HPV16 E6蛋白在宫颈癌中的作用研究进展

Progress on effects of HPV16 E6 on cervical cancer

高危型人乳头状瘤病毒16型(HPV16)与50%以上的宫颈癌密切相关,其E6癌蛋白作为病毒生命周期的主要蛋白之一,在诱导肿瘤发生与发展进程中起重要作用,且与病毒复制、宿主细胞周期调控、细胞凋亡、细胞增殖、细胞恶性表型转化有关。E6蛋白主要作用包括:通过结合E6相关蛋白降解P53抑制细胞凋亡;增强端粒酶活性使宿主细胞永生化;与Daxx启动子区结合,抑制启动子转录活性,降低Daxx蛋白表达,阻遏细胞凋亡;与多种细胞因子相互作用后,经多种途径改变细胞微环境,使之有利于肿瘤细胞逃避宿主固有免疫应答。因此,在宫颈癌的发生和发展中,HPV16 E6蛋白通过多种作用机制发挥重要作用。

High-risk human papillomavirus type 16 （HPV16） causes more than 50% of cervical cancer, its E6 oncoprotein is a major protein in the viral life cycle, and plays a major role in the induction occurrence and development process of tumor. It is also closely related to the viral replication, host cell cycle regulation, apoptosis, cell proliferation and malig- nant phenotype of transformed cells. The main biological functions of E6 protein involve ： degrading P53 and mediating apoptosis by binding the E6-associated protein; enhancing the telomerase activity and inducing immortalization of the host cell; by binding the Daxx promoter binding sites, inhibiting the promoter transcriptional activity and decreasing Daxx expression and repressing apoptosis; after interacting with multiple cytokines, changing the cellular microenvironment to make tumor cells evading the host innate immune response conducting by a variety of ways. Therefore, HPV16 E6 protein plays an important role through a number of mechanisms in the occurrence and development of cervical cancer.