ArticleMolecular and cellular biology1999
Induction of apoptosis by double-stranded-RNA-dependent protein kinase (PKR) involves the alpha subunit of eukaryotic translation initiation factor 2 and NF-kappaB.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 196 citations in OpenAlex.
- PACT suppresses PKR activation through dsRNA binding and dimerization, and is a therapeutic target for triple-negative breast cancer.RNA (New York, N.Y.) · 2025Article
- PANoptosis-related molecular subtype and prognostic model associated with the immune microenvironment and individualized therapy in pancreatic cancer.Frontiers in oncology · 2023Article
- GZ17-6.02 kills prostate cancer cellsFrontiers in oncology · 2022Article
- Formation of Double Stranded RNA Provokes Smooth Muscle Contractions and Structural Modifications in Bladder Ischemia.Research and reports in urology · 2022Article
- Immunogenicity ofAccounts of chemical research · 2021Review
- Regulation of PKR activation and apoptosis during oxidative stress by TRBP phosphorylation.The international journal of biochemistry & cell biology · 2021Article
- The Role of Coronavirus RNA-Processing Enzymes in Innate Immune Evasion.Life (Basel, Switzerland) · 2021Review
- Protein Kinase R in Bacterial Infections: Friend or Foe?Frontiers in immunology · 2021Review
- Prevention of dsRNA-induced interferon signaling by AGO1x is linked to breast cancer cell proliferation.The EMBO journal · 2020Article
- Review
- The location of sensing determines the pancreatic β-cell response to the viral mimetic dsRNA.The Journal of biological chemistry · 2020Article
- NF-κB Activation Promotes Alphavirus Replication in Mature Neurons.Journal of virology · 2019Article
- Potent Anti-hepatitis C Virus (HCV) T Cell Immune Responses Induced in Mice Vaccinated with DNA-Launched RNA Replicons and Modified Vaccinia Virus Ankara-HCV.Journal of virology · 2019Article
- Protein Kinase R Is Constitutively Expressed in the Human Pancreas.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2019Article
- Binding of eEF1A2 to the RNA-dependent protein kinase PKR modulates its activity and promotes tumour cell survival.British journal of cancer · 2018Article
- Expression of the Vaccinia Virus Antiapoptotic F1 Protein Is Blocked by Protein Kinase R in the Absence of the Viral E3 Protein.Journal of virology · 2018Article
- Apoptosis Induction by dsRNA-Dependent Protein Kinase R (PKR) in EPC Cells via Caspase 8 and 9 Pathways.Viruses · 2018Article
- Stress-induced TRBP phosphorylation enhances its interaction with PKR to regulate cellular survival.Scientific reports · 2018Article
- Review
- Review
20 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The double-stranded (ds) RNA-dependent protein kinase (PKR) is a key mediator of antiviral effects of interferon (IFN) and an active player in apoptosis induced by different stimuli. The translation initiation factor eIF-2alpha (alpha subunit of eukaryotic translation initiation factor 2) and IkappaBalpha, the inhibitor of the transcription factor NF-kappaB, have been proposed as downstream mediators of PKR effects. To evaluate the involvement of NF-kappaB and eIF-2alpha in the induction of apoptosis by PKR, we have used vaccinia virus (VV) recombinants that inducibly express PKR concomitantly with a dominant negative mutant of eIF-2alpha or a repressor form of IkappaBalpha. We found that while expression of PKR by a VV vector resulted in extensive inhibition of protein synthesis and induction of apoptosis, coexpression of PKR with a dominant negative mutant of eIF-2alpha (Ser-51-->Ala) reversed both the PKR-mediated translational block and PKR-induced apoptosis. Coexpression of PKR with a repressor form of IkappaBalpha (Ser-32, 36-Ala) also leads to the inhibition of apoptosis by abolishing NF-kappaB induction, while translation remains blocked. Treating cells with two different proteasome inhibitors which block IkappaBalpha degradation, prevented PKR-induced apoptosis, supporting results from coexpression studies. Biochemical analysis and transient assays revealed that PKR expression by a VV vector induced NF-kappaB binding and transactivation. In addition, upregulation of Fas mRNA transcription occurred during PKR activation. Our findings provide direct evidence for the involvement of eIF-2alpha and NF-kappaB in the induction of apoptosis by PKR.
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