A DOUBLE-STRANDED RNA-ACTIVATED PROTEIN KINASE-DEPENDENT PATHWAY MEDIATING STRESS-INDUCED APOPTOSIS

Citation
Sd. Der et al., A DOUBLE-STRANDED RNA-ACTIVATED PROTEIN KINASE-DEPENDENT PATHWAY MEDIATING STRESS-INDUCED APOPTOSIS, Proceedings of the National Academy of Sciences of the United Statesof America, 94(7), 1997, pp. 3279-3283
Citations number
35
Categorie Soggetti
Multidisciplinary Sciences
ISSN journal
00278424
Volume
94
Issue
7
Year of publication
1997
Pages
3279 - 3283
Database
ISI
SICI code
0027-8424(1997)94:7<3279:ADRPKP>2.0.ZU;2-B
Abstract
Apoptosis occurs in response to different cellular stresses, including viral infection, inflammatory cytokines, growth factor deprivation, a nd UV light, but it Is unclear whether these inducers share a common m echanism of induction, The interferon-induced, double-stranded RNA-act ivated protein kinase (PKR) has been implicated in processes that rely on apoptosis as control mechanisms in vivo, including antiviral activ ities, cell growth regulation, and tumorigenesis. Here we report that mouse embryo fibroblasts from mutant mice containing homozygous deleti ons in the PKR gene (Pkr(o/o) mice) were resistant to apoptotic cell d eath in response to double-stranded RNA, tumor necrosis factor-alpha, or lipopolysaccharide, The mechanism underlying the suppression of apo ptosis in the Pkr(o/o) cells could be attributed to defects in the act ivation of DNA-binding activity for the transcription factor interfero n regulatory factor-1 and in Fas mRNA Induction, Thus, these results p rovide genetic evidence implicating a requirement for PKR In mediating different forms of stress-related apoptosis.