Moise Alexander R, Grant Jason R, Vitalis Timothy Z, Jefferies Wilfred A
Biotechnology Laboratory, Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
J Virol. 2002 Feb;76(4):1578-87. doi: 10.1128/jvi.76.4.1578-1587.2002.
E3-6.7K is a small and hydrophobic membrane glycoprotein encoded by the E3 region of subgroup C adenovirus. Recently, E3-6.7K has been shown to be required for the downregulation of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptors by the adenovirus E3/10.4K and E3/14.5K complex of proteins. We demonstrate here that E3-6.7K has additional protective roles, independent of other virus proteins. In transfected Jurkat T-cell lymphoma cells, E3-6.7K was found to maintain endoplasmic reticulum-Ca(2+) homeostasis and inhibit the induction of apoptosis by thapsigargin. The presence of E3-6.7K also lead to a reduction in the TNF-induced release of arachidonic acid from transfected U937 human histiocytic lymphoma cells. In addition, E3-6.7K protected cells against apoptosis induced through Fas, TNF receptor, and TRAIL receptors. Therefore, E3-6.7K confers a wide range of protective effects against both Ca(2+) flux-induced and death receptor-mediated apoptosis.
E3-6.7K是一种由C亚组腺病毒E3区域编码的小的疏水性膜糖蛋白。最近研究表明，腺病毒E3/10.4K和E3/14.5K蛋白复合物下调肿瘤坏死因子（TNF）相关凋亡诱导配体（TRAIL）受体需要E3-6.7K。我们在此证明，E3-6.7K具有独立于其他病毒蛋白的额外保护作用。在转染的Jurkat T细胞淋巴瘤细胞中，发现E3-6.7K可维持内质网-Ca(2+)稳态，并抑制毒胡萝卜素诱导的细胞凋亡。E3-6.7K的存在还导致转染的U937人组织细胞淋巴瘤细胞中TNF诱导的花生四烯酸释放减少。此外，E3-6.7K保护细胞免受通过Fas、TNF受体和TRAIL受体诱导的细胞凋亡。因此，E3-6.7K对Ca(2+)通量诱导的凋亡和死亡受体介导的凋亡均具有广泛的保护作用。
