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Characterization of a functional NF-kappa B site in the human interleukin 1 beta promoter: evidence for a positive autoregulatory loop.
Open accessAbstract
The -300 region of the interleukin 1 beta (IL-1 beta) promoter contains a functional NF-kappa B binding site composed of the decamer sequence 5'-GGGAAAATCC-3'. Probes representing the -300 region or the NF-kappa B site alone interacted with NF-kappa B proteins present in phorbol myristate acetate-, lipopolysaccharide-, or Sendai virus-induced myeloid cell extracts as well as recombinant NFKB1 (p50) and RelA (p65); furthermore, NF-kappa B protein-DNA complex formation was dissociated in vitro by the addition of recombinant I kappa B alpha. Mutation of the NF-kappa B site in the context of the IL-1 beta promoter reduced the responsiveness of the IL-1 beta promoter to various inducers, including phorbol ester, Sendai virus, poly(rI-rC), and IL-1 beta. A 4.4-kb IL-1 beta promoter fragment linked to a chloramphenicol acetyltransferase reporter gene was also preferentially inducible by coexpression of individual NF-kappa B subunits compared with a mutated IL-1 beta promoter fragment. When multiple copies of the IL-1 beta NF-kappa B site were linked to an enhancerless simian virus 40 promoter, this element was able to mediate phorbol ester- or lipopolysaccharide-inducible gene expression. In cotransfection experiments, RelA (p65) and c-Rel (p85) were identified as the main subunits responsible for the activation of the IL-1 beta NF-kappa B site; also, combinations of NFKB1 (p50) and RelA (p65) or c-Rel and RelA were strong transcriptional activators of reporter gene activity. The presence of a functional NF-kappa B binding site in the IL-1 beta promoter suggests that IL-1 positively autoregulates its own synthesis, since IL-1 is a strong inducer of NF-kappa B binding activity. Thus, the IL-1 beta gene may be considered as an important additional member of the family of cytokine genes regulated in part by the NF-kappa B/rel family of transcription factors.
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Metadata
- Authors
- Hiscott, J., Marois, J., Garoufalis, J., D'Addario, M., Roulston, A., Kwan, I., Pepin, N., Lacoste, J., Nguyen, H., & Bensi, G.
- Affiliations
- Lady Davis Institute for Medical Research (CA)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1993-10
- Volume
- 13
- Issue
- 10
- Pages
- 6231-6240
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC364682
- OpenAlex
- W1904705252
- Cited by
- 585
- References
- 68
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 6 · 2023: 19 · 2022: 18 · 2021: 26 · 2020: 24 · 2019: 16 · 2018: 26 · 2017: 20 · 2016: 28 · 2015: 32 · 2014: 22 · 2013: 21 · 2012: 17
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- IL-1β, NF-kappaB binding site, positive autoregulation, RelA/p65, c-Rel, IκBα, transcriptional activation, phorbol ester, lipopolysaccharide, Sendai virus, cytokine gene regulation, transcription factor-DNA complex
- MeSH terms
- Base Sequence, Binding Sites, Cell Line, DNA, Gene Expression Regulation, Humans, Interleukin-1, Molecular Sequence Data, Promoter Regions, Genetic, Proto-Oncogene Proteins, Transcription Factors, Tumor Cells, Cultured, Transcriptional Activation, NF-kappa B, Transcription Factor RelB
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