ArticleMolecular and cellular biology2000
NF-kappaB activation by double-stranded-RNA-activated protein kinase (PKR) is mediated through NF-kappaB-inducing kinase and IkappaB kinase.
Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers.
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Who cites it
171 citing papers in PubMed, 358 citations in OpenAlex.
- DHX36 is a regulatory switch in the interferon-mediated antiviral response.Science advances · 2026Article
- Disruptions of cell signaling pathways in myotonic dystrophy type 1 skeletal muscle, their pathogenic impact, and potential for combinatorial therapeutics.The Journal of biological chemistry · 2026Review
- LincRNA-miR interactions in hepatocellular carcinoma: comprehensive review and in silico analysis: a step toward ncRNA precision.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- 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
- ADARs: pleiotropy in function, versatility in application.Nucleic acids research · 2025Review
- The dsRNA-dependent kinase (PKR) inhibits the growth ofParasitology · 2025Article
- Unravelling the role of protein kinase R (PKR) in neurodegenerative disease: a review.Molecular biology reports · 2025Review
- Protein Kinase R (PKR) as a Novel dsRNA Sensor in Antiviral Innate Immunity.Methods in molecular biology (Clifton, N.J.) · 2025Article
- PKR modulates sterile systemic inflammation-triggered neuroinflammation and brain glucose metabolism disturbances.Frontiers in immunology · 2025Article
- The monkeypox virus-host interplays.Cell insight · 2024Review
- Induction of Viral Mimicry Upon Loss of DHX9 and ADAR1 in Breast Cancer Cells.Cancer research communications · 2024Article
- Induction of viral mimicry upon loss of DHX9 and ADAR1 in breast cancer cells.bioRxiv : the preprint server for biology · 2023Article
- Article
- An integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells.Nature communications · 2023Article
- E3 ligase HECTD3 promotes RNA virus replication and virus-induced inflammation via K33-linked polyubiquitination of PKR.Cell death & disease · 2023Article
- Fingolimod mitigates memory loss in a mouse model of Gulf War Illness amid decreasing the activation of microglia, protein kinase R, and NFκB.Neurotoxicology · 2023Article
- Role of mitochondrial stress and the NLRP3 inflammasome in lung diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Chemotherapy-Induced Senescence Reprogramming Promotes Nasopharyngeal Carcinoma Metastasis by circRNA-Mediated PKR Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Enhancing the immune effect of oHSV-1 therapy through TLR3 signaling in uveal melanoma.Journal of cancer research and clinical oncology · 2023Article
- NS5A domain I antagonises PKR to facilitate the assembly of infectious hepatitis C virus particles.PLoS pathogens · 2023Article
111 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The interferon (IFN)-inducible double-stranded-RNA (dsRNA)-activated serine-threonine protein kinase (PKR) is a major mediator of the antiviral and antiproliferative activities of IFNs. PKR has been implicated in different stress-induced signaling pathways including dsRNA signaling to nuclear factor kappa B (NF-kappaB). The mechanism by which PKR mediates activation of NF-kappaB is unknown. Here we show that in response to poly(rI). poly(rC) (pIC), PKR activates IkappaB kinase (IKK), leading to the degradation of the inhibitors IkappaBalpha and IkappaBbeta and the concomitant release of NF-kappaB. The results of kinetic studies revealed that pIC induced a slow and prolonged activation of IKK, which was preceded by PKR activation. In PKR null cell lines, pIC failed to stimulate IKK activity compared to cells from an isogenic background wild type for PKR in accord with the inability of PKR null cells to induce NF-kappaB in response to pIC. Moreover, PKR was required to establish a sustained response to tumor necrosis factor alpha (TNF-alpha) and to potentiate activation of NF-kappaB by cotreatment with TNF-alpha and IFN-gamma. By coimmunoprecipitation, PKR was shown to be physically associated with the IKK complex. Transient expression of a dominant negative mutant of IKKbeta or the NF-kappaB-inducing kinase (NIK) inhibited pIC-induced gene expression from an NF-kappaB-dependent reporter construct. Taken together, these results demonstrate that PKR-dependent dsRNA induction of NF-kappaB is mediated by NIK and IKK activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.