Accelerated degradation of FADD and procaspase 8 in cells expressing human papilloma virus 16 E6 impairs TRAIL-mediated apoptosis
Accelerated degradation of FADD and procaspase 8 in cells expressing human papilloma virus 16 E6 impairs TRAIL-mediated apoptosis
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DOI：
10.1038/sj.cdd.4401886
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发表时间：
2006-11-01
影响因子：
12.4
通讯作者：
Duerksen-Hughes, P. J.
中科院分区：
文献类型：
--
作者：
Garnett, T. O.;Filippova, M.;Duerksen-Hughes, P. J.
病毒已经发展出复杂的策略来逃避宿主的防御，促进后代的产生和传播。在这项研究中，我们发现将人乳头瘤病毒（HPV） 16e6癌基因转染到HCT116细胞中可以保护细胞免受肿瘤坏死因子相关凋亡诱导配体（TRAIL）介导的凋亡。此外，我们证明E6提供的保护是剂量依赖性的，因为较高水平的E6提供了更大的保护。这种保护机制涉及fas相关死亡结构域（FADD）和caspase 8蛋白水平的快速降低，从而抑制caspase 8、3和2的激活。有趣的是，即使HCT116细胞在TRAIL信号传导方面被归类为II型细胞，E6也不会干扰线粒体凋亡途径。这些发现表明E6对死亡配体的信号传导具有比以前认为的更广泛的作用，并支持E6可以利用不依赖p53的机制来调节细胞存活的观点。
Viruses have developed sophisticated strategies to evade host defenses and facilitate the production and spread of progeny. In this study, we show that transfection of the human papillomavirus (HPV) 16 E6 oncogene into HCT116 cells provides protection from tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. Additionally, we demonstrate that the protection provided by E6 is dose-dependent because higher levels of E6 provide greater protection. The mechanism underlying this protection involves a rapid reduction in the protein levels of both Fas-associated death domain (FADD) and procaspase 8, which results in suppression of the activation of caspases 8, 3 and 2. Interestingly, E6 does not interfere with the mitochondrial apoptotic pathway even though HCT116 cells have been classified as type II cells with regard to TRAIL signaling. These findings demonstrate that E6 has a more generalized effect on signaling by death ligands than was previously thought and support the notion that E6 can utilize p53-independent mechanisms to modulate cell survival.