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Cited by 77interferon and immune responsesCytokine Signaling Pathways and InteractionsImmune Response and Inflammation

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Identification and characterization of an interferon (IFN)-stimulated response element-IFN-stimulated gene factor 3-independent signaling pathway for IFN-alpha.

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Haque, S.J., Williams, B.R.·1994·Journal of Biological Chemistry
DOI 10.1016/s0021-9258(17)32200-7
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Abstract

Transcriptional activation of genes containing the interferon (1FN)-stimulated response element (ISRE) by IFN-a is known to be mediated through the post-translational activation of IFN-stimulated gene factor 3 (ISGF3) and its subsequent interactions with the ISRE. W e have identified an ISRE-ISGF34ndependent signaling pathway used by IFN-a for the induction of the IFN regulatory factor 1 (IRF-1) gene. A minimal functional promoter of the IRF-1 gene does not contain an ISRE, but we have shown that transcription of the IRF-1 gene is activated by IFN-a in cell lines that do not produce ISGF3 activity due to the absence of functional ISGF3-7 (p48) polypeptide. This ISRE-ISGF3-independent pathway for IFN-a signaling involves a cis-acting enhancer element located in the IRF-1 promoter, termed the inverted repeat (IR) element, and its cognate trans-acting factor, IR-binding factor a (IRBF-a). IFN-y also activates a transcription factor(s) that forms a different complex (IRBF-7) with the IR element. Protein-tyrosine kinase (tyk2) activity is required for the induction of IRBF-a, but not IRBF-7. The p91 subunit of ISGF3 is necessary for the formation of both IRBF-a and IRBF-7.Interferons (IFNs)' constitute a heterogeneous family of cytokines, originally identified as antiviral agents.Subsequent studies have shown that IFNs can function as regulators of different biological responses, namely, cellular growth, differentiation, and immune functions (14).Type I IFNs (a and p)

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Metadata

Authors
Haque, S. J., & Williams, B. R.
Affiliations
Cleveland Clinic (US)
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1994-07
Volume
269
Issue
30
Pages
19523-19529
ISSN
0021-9258 (ISSN-L)
DOI
10.1016/s0021-9258(17)32200-7
OpenAlex
W1510740341
Cited by
77
References
0
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 1 · 2013: 1 · 2012: 1
FWCI
2.40
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Medical Research Council Canada
  • Medical Research Council
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
interferon-alpha, interferon-stimulated response element, interferon-gamma, cis-acting enhancer, transcriptional activation
MeSH terms
Base Sequence, Cells, Cultured, DNA-Binding Proteins, Gene Expression Regulation, Humans, Molecular Sequence Data, Phosphorylation, Protein Binding, Protein-Tyrosine Kinases, Regulatory Sequences, Nucleic Acid, Transcription Factors, Transcription, Genetic, Signal Transduction, Trans-Activators, Interferon-alpha, STAT1 Transcription Factor

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