Howie Heather L, Katzenellenbogen Rachel A, Galloway Denise A
Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Virology. 2009 Feb 20;384(2):324-34. doi: 10.1016/j.virol.2008.11.017. Epub 2008 Dec 10.
The papillomaviruses are small DNA viruses that encode approximately eight genes, and require the host cell DNA replication machinery for their viral DNA replication. Thus papillomaviruses have evolved strategies to induce host cell DNA synthesis balanced with strategies to protect the cell from unscheduled replication. While the papillomavirus E1 and E2 genes are directly involved in viral replication by binding to and unwinding the origin of replication, the E6 and E7 proteins have auxillary functions that promote proliferation. As a consequence of disrupting the normal checkpoints that regulate cell cycle entry and progression, the E6 and E7 proteins play a key role in the oncogenic properties of human papillomaviruses with a high risk of causing anogenital cancers (HR HPVs). As a consequence, E6 and E7 of HR HPVs are invariably expressed in cervical cancers. This article will focus on the E6 protein and its numerous activities including inactivating p53, blocking apoptosis, activating telomerase, disrupting cell adhesion, polarity and epithelial differentiation, altering transcription and reducing immune recognition.
乳头瘤病毒是小型DNA病毒,编码约8个基因,其病毒DNA复制需要宿主细胞的DNA复制机制。因此,乳头瘤病毒已进化出诱导宿主细胞DNA合成的策略,并与保护细胞免受非计划复制的策略保持平衡。乳头瘤病毒E1和E2基因通过与复制起点结合并解开双链直接参与病毒复制,而E6和E7蛋白具有促进增殖的辅助功能。由于破坏了调节细胞周期进入和进程的正常检查点,E6和E7蛋白在具有引起肛门生殖器癌症高风险的人乳头瘤病毒(HR HPV)的致癌特性中起关键作用。因此,HR HPV的E6和E7在宫颈癌中总是表达的。本文将重点关注E6蛋白及其众多活性,包括使p53失活、阻断细胞凋亡、激活端粒酶、破坏细胞黏附、极性和上皮分化、改变转录以及降低免疫识别。