Demers G W, Espling E, Harry J B, Etscheid B G, Galloway D A
Program in Cancer Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98040, USA.
J Virol. 1996 Oct;70(10):6862-9. doi: 10.1128/JVI.70.10.6862-6869.1996.
Cells arrest in the G1 or G0 phase of the cell cycle in response to a variety of negative growth signals that induce arrest by different molecular pathways. The ability of human papillomavirus (HPV) oncogenes to bypass these signals and allow cells to progress into the S phase probably contributes to the neoplastic potential of the virus. The E7 protein of HPV-16 was able to disrupt the response of epithelial cells to three different negative growth arrest signals: quiescence imposed upon suprabasal epithelial cells, G1 arrest induced by DNA damage, and inhibition of DNA synthesis caused by treatment with transforming growth factor beta. The same set of mutated E7 proteins was able to abrogate all three growth arrest signals. Mutant proteins that failed to abrogate growth arrest signals were transformation deficient and included E7 proteins that bound retinoblastoma protein in vitro. In contrast, HPV-16 E6 was able to bypass only DNA damage-induced G1 arrest, not suprabasal quiescence or transforming growth factor beta-induced arrest. The E6 and E7 proteins from the low-risk virus HPV-6 were not able to bypass any of the growth arrest signals.
细胞会因多种负性生长信号而停滞在细胞周期的G1期或G0期，这些信号通过不同的分子途径诱导细胞停滞。人乳头瘤病毒（HPV）癌基因绕过这些信号并使细胞进入S期的能力可能有助于该病毒的致瘤潜能。HPV - 16的E7蛋白能够破坏上皮细胞对三种不同负性生长停滞信号的反应：施加于基底上层上皮细胞的静止状态、由DNA损伤诱导的G1期停滞以及用转化生长因子β处理导致的DNA合成抑制。同一组突变的E7蛋白能够消除所有三种生长停滞信号。未能消除生长停滞信号的突变蛋白缺乏转化能力，包括在体外能结合视网膜母细胞瘤蛋白的E7蛋白。相比之下，HPV - 16 E6仅能绕过由DNA损伤诱导的G1期停滞，而不能绕过基底上层静止状态或转化生长因子β诱导的停滞。低风险病毒HPV - 6的E6和E7蛋白不能绕过任何生长停滞信号。
