ArticleMolecular and cellular biology2009
TRBP control of PACT-induced phosphorylation of protein kinase R is reversed by stress.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
- Multiple Inhibitory Factors Act in the Late Phase of HIV-1 Replication: a Systematic Review of the Literature.Microbiology and molecular biology reviews : MMBR · 2018Pooled it
- Cigarette Smoke Induces Canonical Stress Granule Formation in Human Bronchial Epithelial Cells in Reactive Oxygen Species- and PERK-Dependent Manners.Biomolecules · 2026Article
- Deciphering the multifaceted role of double-stranded RNA sensor protein kinase R: pathophysiological function beyond the antiviral response.RNA biology · 2025Review
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- Mutation in Prkra results in cerebellar abnormality and reduced eIF2α phosphorylation in a model of DYT-PRKRA.Disease models & mechanisms · 2024Article
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- A frameshift mutation in the murinebioRxiv : the preprint server for biology · 2024Article
- Caspase-mediated processing of TRBP regulates apoptosis during viral infection.Nucleic acids research · 2024Article
- The helicase domain of human Dicer prevents RNAi-independent activation of antiviral and inflammatory pathways.The EMBO journal · 2024Article
- RNA recognition by PKR during DNA virus infection.Journal of medical virology · 2024Review
- Innate immune responses to RNA: sensing and signaling.Frontiers in immunology · 2024Review
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- Retrotransposon LINE-1 bodies in the cytoplasm of piRNA-deficient mouse spermatocytes: Ribonucleoproteins overcoming the integrated stress response.PLoS genetics · 2023Article
- Peste Des Petits Ruminants Virus Nucleocapsid Protein Interacts with Protein Kinase R-Activating Protein and Induces Stress Granules To Promote Viral Replication.Journal of virology · 2023Article
- A tale of two proteins: PACT and PKR and their roles in inflammation.The FEBS journal · 2021Review
- Regulation of PKR activation and apoptosis during oxidative stress by TRBP phosphorylation.The international journal of biochemistry & cell biology · 2021Article
- Human DICER helicase domain recruits PKR and modulates its antiviral activity.PLoS pathogens · 2021Article
- Opposite actions of two dsRNA-binding proteins PACT and TRBP on RIG-I mediated signaling.The Biochemical journal · 2021Article
- RNA Granules in Antiviral Innate Immunity: A Kaposi's Sarcoma-Associated Herpesvirus Journey.Frontiers in microbiology · 2021Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
The TAR RNA binding Protein, TRBP, inhibits the activity of the interferon-induced protein kinase R (PKR), whereas the PKR activator, PACT, activates its function. TRBP and PACT also bind to each other through their double-stranded RNA binding domains (dsRBDs) and their Medipal domains, which may influence their activity on PKR. In a human immunodeficiency virus (HIV) long terminal repeat-luciferase assay, PACT unexpectedly reversed PKR-mediated inhibition of gene expression. In a translation inhibition assay in HeLa cells, PACT lacking the 13 C-terminal amino acids (PACTDelta13), but not full-length PACT, activated PKR and enhanced interferon-mediated repression. In contrast, in the astrocytic U251MG cells that express low TRBP levels, both proteins activate PKR, but PACTDelta13 is stronger. Immunoprecipitation assays and yeast two-hybrid assays show that TRBP and PACTDelta13 interact very weakly due to a loss of binding in the Medipal domain. PACT-induced PKR phosphorylation was restored in Tarbp2(-/-) murine tail fibroblasts and in HEK293T or HeLa cells when TRBP expression was reduced by RNA interference. In HEK293T and HeLa cells, arsenite, peroxide, and serum starvation-mediated stresses dissociated the TRBP-PACT interaction and increased PACT-induced PKR activation, demonstrating the relevance of this control in a physiological context. Our results demonstrate that in cells, TRBP controls PACT activation of PKR, an activity that is reversed by stress.
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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.