MALIGNANT TRANSFORMATION BY A MUTANT OF THE IFN-INDUCIBLE DSRNA-DEPENDENT PROTEIN-KINASE
MALIGNANT TRANSFORMATION BY A MUTANT OF THE IFN-INDUCIBLE DSRNA-DEPENDENT PROTEIN-KINASE
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DOI：
10.1126/science.1382315
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发表时间：
1992-09-18
期刊：
影响因子：
56.9
通讯作者：
SONENBERG, N
中科院分区：
文献类型：
--
作者：
KOROMILAS, AE;ROY, S;SONENBERG, N
双链RNA依赖性蛋白激酶（dsRNA-PK）被认为是干扰素（IFN）抗病毒和抗增殖作用的关键介质。研究激酶的生理功能表明，它通过调节蛋白质合成参与细胞生长和分化。dsRNA-PK在体外和体内的自磷酸化和随后的激活导致真核起始因子-2（eIF-2）的α亚基的磷酸化和蛋白质合成的抑制。在NIH 3 T3细胞中表达功能缺陷的人dsRNA-PK突变体导致恶性转化，表明dsRNA-PK可能作为细胞增殖和肿瘤发生的抑制剂。
The double-stranded RNA-dependent protein kinase (dsRNA-PK) is thought to be a key mediator of the antiviral and antiproliferative effects of interferons (IFNs). Studies examining the physiological function of the kinase suggest that it participates in cell growth and differentiation by regulating protein synthesis. Autophosphorylation and consequent activation of dsRNA-PK in vitro and in vivo result in phosphorylation of the alpha-subunit of eukaryotic initiation factor-2 (eIF-2) and inhibition of protein synthesis. Expression of a functionally defective mutant of human dsRNA-PK in NIH 3T3 cells resulted in malignant transformation, suggesting that dsRNA-PK may function as a suppressor of cell proliferation and tumorigenesis.