A double-stranded RNA-activated protein kinase-dependent pathway mediating stress-induced apoptosis
Open accessAbstract
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-α, 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.
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Activation of PKR can either induce apoptotic cell death or at least enhance this process when apoptosis is initiated by other agents.
“Several studies established that activation of PKR can either induce apoptotic cell death or at least enhance this process when apoptosis is initiated by other agents [61, 62].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [62]
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PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease
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- Authors
- Der, S. D., Yang, Y.-L., Weissmann, C., & Williams, B. R. G.
- Affiliations
- Cleveland Clinic (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1997-04
- Volume
- 94
- Issue
- 7
- Pages
- 3279-3283
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC20360
- OpenAlex
- W2166497605
- Cited by
- 389
- References
- 2
- Citations by year
- 2026: 1 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 1 · 2019: 4 · 2018: 1 · 2017: 5 · 2016: 3 · 2015: 6 · 2014: 5 · 2013: 6 · 2012: 9
- FWCI
- 12.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI 34039-02, R01AI034039)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- double-stranded RNA-dependent protein kinase, PKR, stress-induced apoptosis, IRF1, TNF-α, lipopolysaccharide, double-stranded RNA, mouse embryonic fibroblasts, interferon signaling, antiviral defense
- MeSH terms
- Animals, DNA-Binding Proteins, HeLa Cells, Humans, Phosphoproteins, RNA, Double-Stranded, RNA, Messenger, Stress, Physiological, Apoptosis, Protein Serine-Threonine Kinases, Mice, Knockout, fas Receptor, eIF-2 Kinase, Interferon Regulatory Factor-1, Mice
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