ArticleMolecular and cellular biology2002
Multiple regulatory domains of IRF-5 control activation, cellular localization, and induction of chemokines that mediate recruitment of T lymphocytes.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
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Who cites it
114 citing papers in PubMed, 250 citations in OpenAlex.
- Inhibition of IRF5 hyperactivation protects from lupus onset and severity.The Journal of clinical investigation · 2020Trial
- TLR-induced STK25 activation promotes IRF5-mediated inflammation.Life science alliance · 2025Article
- Identification of an IRF8 gene in common carp (Cyprinus carpio. L) and its regulatory role in immune responses.BMC veterinary research · 2025Article
- Interferon regulatory factor 5: a potential target for therapeutic intervention in inflammatory diseases.Frontiers in immunology · 2025Review
- Fine-mapping and molecular characterisation of primary sclerosing cholangitis genetic risk loci.Nature communications · 2024Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- Breast Cancer Stem Cells Upregulate IRF6 in Stromal Fibroblasts to Induce Stromagenesis.Cells · 2024Article
- IRF5 mediates adaptive immunity via altered glutamine metabolism, mTORC1 signaling and post-transcriptional regulation following T cell receptor activation.bioRxiv : the preprint server for biology · 2024Article
- Role of interferon regulatory factor 5 (IRF5) in tumor progression: Prognostic and therapeutic potential.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- Cytoplasmic localization of IRF5 induces Wnt5a/E-cadherin degradation and promotes gastric cancer cells metastasis.Cancer gene therapy · 2023Article
- Sex differences in the percentage of IRF5 positive B cells are associated with higher production of TNF-α in women in response to TLR9 in humans.Biology of sex differences · 2023Article
- Frequency of IRF5+ dendritic cells is associated with the TLR7-induced inflammatory cytokine response in SARS-CoV-2 infection.Cytokine · 2023Article
- Promoter Binding and Nuclear Retention Features of Zebrafish IRF Family Members in IFN Response.Frontiers in immunology · 2022Article
- Defactinib inhibits PYK2 phosphorylation of IRF5 and reduces intestinal inflammation.Nature communications · 2021Article
- Article
- Coordination between innate immune cells, type I IFNs and IRF5 drives SLE pathogenesis.Cytokine · 2020Review
- T Cell-Intrinsic IRF5 Regulates T Cell Signaling, Migration, and Differentiation and Promotes Intestinal Inflammation.Cell reports · 2020Article
- Inhibition of IRF5 cellular activity with cell-penetrating peptides that target homodimerization.Science advances · 2020Article
- IRF5 Promotes Influenza Virus-Induced Inflammatory Responses in Human Induced Pluripotent Stem Cell-Derived Myeloid Cells and Murine Models.Journal of virology · 2020Article
- Interferon Regulatory Factor-5 in Resident Macrophage Promotes Polycystic Kidney Disease.Kidney360 · 2020Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Transcription factors of the interferon regulatory factor (IRF) family have been identified as critical mediators of early inflammatory gene transcription in infected cells. We recently determined that, besides IRF-3 and IRF-7, IRF-5 serves as a direct transducer of virus-mediated signaling. In contrast to that mediated by the other two IRFs, IRF-5-mediated activation is virus specific. We show that, in addition to Newcastle disease virus (NDV) infection, vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1) infection activates IRF-5, leading to the induction of IFNA gene subtypes that are distinct from subtypes induced by NDV. The IRF-5-mediated stimulation of inflammatory genes is not limited to IFNA since in BJAB/IRF-5-expressing cells IRF-5 stimulates transcription of RANTES, macrophage inflammatory protein 1 beta, monocyte chemotactic protein 1, interleukin-8, and I-309 genes in a virus-specific manner. By transient- transfection assay, we identified constitutive-activation (amino acids [aa] 410 to 489) and autoinhibitory (aa 490 to 539) domains in the IRF-5 polypeptide. We identified functional nuclear localization signals (NLS) in the amino and carboxyl termini of IRF-5 and showed that both of these NLS are sufficient for nuclear translocation and retention in infected cells. Furthermore, we demonstrated that serine residues 477 and 480 play critical roles in the response to NDV infection. Mutation of these residues from serine to alanine dramatically decreased phosphorylation and resulted in a substantial loss of IRF-5 transactivation in infected cells. Thus, this study defines the regulatory phosphorylation sites that control the activity of IRF-5 in NDV-infected cells and provides further insight into the structure and function of IRF-5. It also shows that the range of IRF-5 immunoregulatory target genes includes members of the cytokine and chemokine superfamilies.
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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.