New York University School of Medicine, New York 10016.
J Gen Physiol. 1970 Jul 1;56(1):76-89. doi: 10.1085/jgp.56.1.76.
Rabbit kidney cell cultures stimulated with either double-stranded polyinosinate-polycytidylate (poly I:poly C) or with ultraviolet-irradiated Newcastle disease virus (UV-NDV) produce two types of interferon response, designated "early" and "late," respectively. The early response is suppressed by inhibitors of RNA or protein synthesis and is therefore thought to represent de novo synthesis of interferon. Circumstantial evidence suggested that this interferon response is regulated by a translation control mechanism. Late interferon production with poly I:poly C only took place in the presence of inhibitors of RNA or protein synthesis. The late interferon is therefore likely to be derived by the activation of an interferon precursor. The stimulation of late poly I:poly C-induced interferon production by cycloheximide suggested the existence of a second, posttranslational level of control of interferon production. This posttranslation control seems to be activated by interferon. UV-NDV can probably suppress the synthesis of the posttranslation inhibitory protein, and therefore it stimulates a late interferon response in the absence of inhibitors of RNA or protein synthesis. It is postulated that both the translation and posttranslation inhibitor participate in the development of a cellular refractory state to repeated interferon stimulation. The picture of interferon which emerges from this study is one of a heterogenous class of proteins whose production is controlled by cellular repressors acting at various levels.
兔肾细胞培养物用双链聚肌苷酸-聚胞苷酸(poly I:poly C)或用紫外线照射的新城疫病毒(UV-NDV)刺激,分别产生两种类型的干扰素反应,分别称为“早期”和“晚期”。早期反应被 RNA 或蛋白质合成抑制剂所抑制,因此被认为代表干扰素的从头合成。间接证据表明,这种干扰素反应受翻译控制机制调节。只有在用 RNA 或蛋白质合成抑制剂存在的情况下,才能用 poly I:poly C 诱导晚期干扰素的产生。因此,晚期干扰素可能是由干扰素前体的激活产生的。环已亚硝脲对 poly I:poly C 诱导的晚期干扰素产生的刺激表明,干扰素产生存在第二个翻译后水平的控制。这种翻译后控制似乎是由干扰素激活的。UV-NDV 可能抑制翻译后抑制蛋白的合成,因此在没有 RNA 或蛋白质合成抑制剂的情况下,它会刺激晚期干扰素反应。据推测,翻译和翻译后抑制剂都参与了细胞对重复干扰素刺激产生抗性的发展。本研究中出现的干扰素图像是一类具有不同性质的蛋白质,其产生受作用于不同水平的细胞抑制剂控制。