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Cited by 413Cytokine Signaling Pathways and InteractionsNF-κB Signaling Pathwaysinterferon and immune responses

Synergy between Interferon-γ and Tumor Necrosis Factor-α in Transcriptional Activation Is Mediated by Cooperation between Signal Transducer and Activator of Transcription 1 and Nuclear Factor κB

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Ohmori, Yoshihiro, Schreiber, Robert D., Hamilton, Thomas A.·1997·Journal of Biological Chemistry
DOI 10.1074/jbc.272.23.14899
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Abstract

Interferon-gamma (IFNgamma) and tumor necrosis factor-alpha (TNFalpha) cooperate to induce the expression of many gene products during inflammation. The present report demonstrates that a portion of this cooperativity is mediated by synergism between two distinct transcription factors: signal transducer and activator of transcription 1 (STAT1) and nuclear factor kappaB (NF-kappaB). IFNgamma and TNFalpha synergistically induce expression of mRNAs encoding interferon regulatory factor-1 (IRF-1), intercellular adhesion molecule-1, Mig (monokine induced by gamma-interferon), and RANTES (regulated on activation normal T cell expressed and secreted) in normal but not STAT1-deficient mouse fibroblasts, indicating a requirement for STAT1. Transient transfection assays in fibroblasts using site-directed mutants of a 1.3-kilobase pair sequence of the IRF-1 gene promoter revealed that the synergy was dependent upon two sequence elements; a STAT binding element and a kappaB motif. Artificial constructs containing a single copy of both a STAT binding element and a kappaB motif linked to the herpes virus thymidine kinase promoter were able to mediate synergistic response to IFNgamma and TNFalpha; such response varied with both the relative spacing and the specific sequence of the regions between these two sites. Cooperatively responsive sequence constructs bound both STAT1alpha and NF-kappaB in nuclear extracts prepared from IFNgamma- and/or TNFalpha-stimulated fibroblasts, although bindin…

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Crossref · 10.1074/jbc.272.23.14899

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  • Although STATs bind a similar DNA binding site, they may interact with co-activators or co-repressors to regulate different sets of their own downstream targets.

    “Although they bind to a similar DNA binding site, STATs may interact with co-activator or co-repressor to regulate different sets of their own downstream targets (5”

    From STAT3 Contributes to the Mitogenic Response of Hepatocytes during Liver Regeneration (2002) · cites this paper as [39]

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Authors
Ohmori, Y., Schreiber, R. D., & Hamilton, T. A.
Affiliations
  • Cleveland Clinic (US)
  • Washington University in St. Louis (US)
Corresponding author
Ohmori, Yoshihiro
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1997-06
Volume
272
Issue
23
Pages
14899-14907
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.272.23.14899
OpenAlex
W2014237818
Cited by
413
References
2
Citations by year
2026: 8 · 2025: 7 · 2024: 7 · 2023: 7 · 2022: 16 · 2021: 7 · 2020: 10 · 2019: 9 · 2018: 7 · 2017: 6 · 2016: 7 · 2015: 12 · 2014: 15 · 2013: 13 · 2012: 9
FWCI
10.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (CA62220, P01CA062220)
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords
interferon-gamma, TNF-α, STAT1, NF-κB, transcriptional synergy, IRF1, promoter regulation, ICAM-1, MIG, RANTES, inflammatory gene expression, transcription factor cooperation
MeSH terms
Animals, Cells, Cultured, DNA-Binding Proteins, Drug Synergism, Fibroblasts, Interferon-gamma, Mice, Mutant Strains, Phosphoproteins, Promoter Regions, Genetic, Recombinant Fusion Proteins, Recombinant Proteins, RNA, Messenger, Transcription Factors, Transcription, Genetic, Transfection, Tumor Necrosis Factor-alpha, Signal Transduction, Transcriptional Activation, Trans-Activators, Polymerase Chain Reaction, NF-kappa B, 3T3 Cells, Genes, Reporter, Intercellular Adhesion Molecule-1, Chemokines, Chemokine CCL5, Chemokines, CXC, Intercellular Signaling Peptides and Proteins, STAT1 Transcription Factor, Interferon Regulatory Factor-1, Mice, Chemokine CXCL9

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