Induction of apoptosis by the dsRNA-dependent protein kinase (PKR): Mechanism of action
Induction of apoptosis by the dsRNA-dependent protein kinase (PKR): Mechanism of action
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DOI：
10.1023/a:1009664109241
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发表时间：
2000-04-01
期刊：
影响因子：
7.2
通讯作者：
Esteban, M
中科院分区：
文献类型：
--
作者：
Gil, J;Esteban, M
干扰素是一个细胞因子家族，通过诱导一组复杂的蛋白质发挥抗病毒、抗肿瘤和免疫调节作用。最著名的IFN诱导蛋白之一是dsRNA依赖性蛋白激酶（PKR），其介导抗病毒和抗细胞活性。PKR通过起始因子eIF-2的α亚基（eIF-2 α）的磷酸化来抑制翻译起始，并且还控制几种转录因子如NF-κ B、p53或STAT的活化。此外，PKR介导由许多不同刺激诱导的细胞凋亡，例如用LPS、TNF-α、病毒感染或血清饥饿处理。PKR诱导细胞凋亡的机制涉及eIF-2 α的磷酸化和NF-κ B的活化。通过这种方式，PKR调节不同基因的表达。在响应PKR而上调的基因中有Fas、Bax和p53。PKR诱导的细胞凋亡的途径涉及FADD通过独立于Fas和TNFR的机制激活caspase 8。由于干扰素被用作不同疾病的药物，如病毒感染和癌症，了解PKR引发的细胞凋亡诱导的途径应该是有用的IFN治疗的合理设计。
Interferons are a family of cytokines that exerts antiviral, antitumor and immunomodulatory actions by inducing a complex set of proteins. One of the best known IFN-induced protein is the dsRNA-dependent protein kinase (PKR), that mediates both antiviral and anticellular activities. PKR inhibits translation initiation through the phosphorylation of the alpha subunit of the initiation factor eIF-2 (eIF-2 alpha) and also controls the activation of several transcription factors such as NF-kappa B, p53, or STATs. In addition, PKR mediates apoptosis induced by many different stimuli, such as treatment with LPS, TNF-alpha, viral infection, or serum starvation. The mechanism of apoptosis induction by PKR involves phosphorylation of eIF-2 alpha and activation of NF-kappa B. In this way, expression of different genes is regulated by PKR. Among the genes upregulated in response to PKR are Fas, Bax and p53. The pathway of PKR-induced apoptosis involves FADD activation of caspase 8 by a mechanism independent of Fas and TNFR. Since IFNs are used as drugs for different disorders such as viral infection and cancer, understanding the pathway of apoptosis induction triggered by PKR should be useful in the rational design of IFN therapies.