Jiang P H, Chany-Fournier F, Galabru J, Robert N, Hovanessian A G, Chany C
Institut National de la Santé de la Recherche Médicale, Unité 43, Hôpital Saint Vincent de Paul.
J Biol Chem. 1988 Dec 15;263(35):19154-8.
Interferons, via specific membrane-bound receptors, induce various cellular functions of which antiviral protection is the most extensively studied. We have previously reported the existence of interferon antagonists (referred to as sarcolectins) in various tissue extracts from placental blood, cartilage, brain, muscle, or from sarcomas. These sarcolectins have been fully characterized and purified to homogeneity. In interferon-treated cells, they restore virus sensitivity 4-6 h after the establishment of antiviral protection. In the present study we investigate the effect of sarcolectins on the steady state levels of two double-stranded RNA dependent enzymes, 2-5A (p chi (A2'p)nA) synthetase and protein kinase. Several authors have previously emphasized the role of these enzymes in the mechanism of interferon's antiviral action. Interferon promotes a 4-8 fold increase in protein kinase and 2-5A synthetase in cells. Addition of sarcolectin 5 h after interferon results in a dramatic reduction in the steady state levels of both these enzymes, as shown by their decreased activity and yield observed in Western blot assays. The degradation of the antiviral response in sarcolectin-treated cells might therefore be at least partially attributed to a reduced synthesis of protein kinase and 2-5A synthetase. Since there are no direct interactions between sarcolectins and interferon or its receptors, it can be postulated that sarcolectins exert their effect through these interferon-dependent proteins. We postulate that the opposing biological effects of interferon and sarcolectins strike a balance which may, however, be modified in one direction or the other, depending on their respective concentrations.
干扰素通过特定的膜结合受体诱导多种细胞功能，其中抗病毒保护是研究最为广泛的。我们之前报道过在胎盘血、软骨、脑、肌肉或肉瘤的各种组织提取物中存在干扰素拮抗剂（称为肌集蛋白）。这些肌集蛋白已得到充分表征并纯化至同质。在经干扰素处理的细胞中，它们在建立抗病毒保护4 - 6小时后恢复病毒敏感性。在本研究中，我们研究了肌集蛋白对两种双链RNA依赖性酶，即2 - 5A（p chi (A2'p)nA）合成酶和蛋白激酶稳态水平的影响。几位作者之前强调了这些酶在干扰素抗病毒作用机制中的作用。干扰素可使细胞中的蛋白激酶和2 - 5A合成酶增加4 - 8倍。在干扰素作用5小时后添加肌集蛋白会导致这两种酶的稳态水平显著降低，这在蛋白质印迹分析中表现为它们活性和产量的下降。因此，在经肌集蛋白处理的细胞中抗病毒反应的降解可能至少部分归因于蛋白激酶和2 - 5A合成酶合成的减少。由于肌集蛋白与干扰素或其受体之间不存在直接相互作用，可以推测肌集蛋白通过这些依赖干扰素的蛋白质发挥作用。我们推测，干扰素和肌集蛋白相反的生物学效应达到了一种平衡，然而，这种平衡可能会根据它们各自的浓度向一个方向或另一个方向改变。
