A Novel Interferon Regulatory Factor Family Transcription Factor, ICSAT/Pip/LSIRF, That Negatively Regulates the Activity of Interferon-Regulated Genes
Open accessAbstract
We have isolated a novel cDNA clone encoding interferon (IFN) consensus sequence-binding protein in adult T-cell leukemia cell line or activated T cells (ICSAT); this protein is the human homolog of the recently cloned Pip/LSIRF. ICSAT is structurally most closely related to the previously cloned ICSBP, a member of the IFN regulatory factor (IRF) family of proteins that binds to interferon consensus sequences (ICSs) found in many promoters of the IFN-regulated genes. Among T-cell lines investigated, ICSAT was abundantly expressed in human T-cell leukemia virus type 1 (HTLV-1)-infected T cells. When the HTLV-1 tax gene was expressed or phorbol myristake acetate-A23187 stimulation was used, ICSAT expression was induced in Jurkat cells which otherwise do not express ICSAT. When the binding of ICSAT to four different ICSs was tested, the relative differences in binding affinities for those ICSs were determined. To study the functional role of ICSAT, we performed cotransfection experiments with the human embryonal carcinoma cell line N-Tera2. ICSAT was demonstrated to possess repressive function over the gene activation induced by IFN stimulation or by IRF-1 cotransfection. Such repressive function is similar to that seen in IRF-2 or ICSBP. However, we have found that ICSAT has a different repressive effect from that of IRF-2 or ICSBP in some IFN-responsive reporter constructs. These results suggest that a novel mechanism of gene regulation by "differential repression" is used by multiple members of repressor proteins with different repressive effects on the IFN-responsive genes.
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- Authors
- Yamagata, T., Nishida, J., Tanaka, T., Sakai, R., Mitani, K., Yoshida, M., Taniguchi, T., Yazaki, Y., & Hirai, H.
- Affiliations
- The University of Tokyo (JP)
- Teikyo University (JP)
- Jichi Medical University (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1996-04-01
- Volume
- 16
- Issue
- 4
- Pages
- 1283-1294
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC231112
- OpenAlex
- W2110972790
- Cited by
- 196
- References
- 75
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 1 · 2022: 6 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 4 · 2014: 1 · 2013: 8 · 2012: 4
- FWCI
- 7.40
- 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 › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- interferon-regulated genes, transcriptional repression, IRF8, IRF2, HTLV-1, tax gene, T-cell leukemia, gene expression regulation, repressor protein
- MeSH terms
- Calcimycin, Interferon Regulatory Factor-8, Interferon Regulatory Factor-4, Amino Acid Sequence, Animals, Base Sequence, Carrier Proteins, DNA-Binding Proteins, Gene Expression Regulation, Humans, Interferons, Lymphocyte Activation, Molecular Sequence Data, Repressor Proteins, T-Lymphocytes, Tetradecanoylphorbol Acetate, Transcription Factors, Tumor Cells, Cultured, Leukemia, T-Cell, Transcriptional Activation, Genes, pX, Consensus Sequence, Sequence Homology, Amino Acid, DNA, Complementary, Interferon Regulatory Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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