A double-stranded RNA-activated protein kinase-dependent pathway mediating stress-induced apoptosis

被引:357
|
作者
Der, SD
Yang, YL
Weissmann, C
Williams, BRG
机构
[1] UNIV ZURICH,INST MOL BIOL 1,CH-8093 ZURICH,SWITZERLAND
[2] CLEVELAND CLIN FDN,RES INST,DEPT CANC BIOL,CLEVELAND,OH 44195
关键词
D O I
10.1073/pnas.94.7.3279
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Apoptosis occurs in response to different cellular stresses, including viral infection, inflammatory cytokines, growth factor deprivation, and UV light, but it Is unclear whether these inducers share a common mechanism of induction, The interferon-induced, double-stranded RNA-activated protein kinase (PKR) has been implicated in processes that rely on apoptosis as control mechanisms in vivo, including antiviral activities, cell growth regulation, and tumorigenesis. Here we report that mouse embryo fibroblasts from mutant mice containing homozygous deletions in the PKR gene (Pkr(o/o) mice) were resistant to apoptotic cell death in response to double-stranded RNA, tumor necrosis factor-alpha, or lipopolysaccharide, The mechanism underlying the suppression of apoptosis in the Pkr(o/o) cells could be attributed to defects in the activation of DNA-binding activity for the transcription factor interferon regulatory factor-1 and in Fas mRNA Induction, Thus, these results provide genetic evidence implicating a requirement for PKR In mediating different forms of stress-related apoptosis.
引用
收藏
页码:3279 / 3283
页数:5
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