Induction of a Unique Isoform of the NCOA7 Oxidation Resistance Gene by Interferon β-1b
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We demonstrate that interferon (IFN)-β-1b induces an alternative-start transcript containing the C-terminal TLDc domain of nuclear receptor coactivator protein 7 (NCOA7), a member of the OXR family of oxidation resistance proteins. IFN-β-1b induces NCOA7-AS (alternative start) expression in peripheral blood mononuclear cells (PBMCs) obtained from healthy individuals and multiple sclerosis patients and human fetal brain cells, astrocytoma, neuroblastoma, and fibrosarcoma cells. NCOA7-AS is a previously undocumented IFN-β-inducible gene that contains only the last 5 exons of full-length NCOA7 plus a unique first exon (exon 10a) that is not found in longer forms of NCOA7. This exon encodes a domain closely related to an important class of bacterial aldo-keto oxido-reductase proteins that play a critical role in regulating redox activity. We demonstrate that NCOA7-AS is induced by IFN and LPS, but not by oxidative stress and exhibits, independently, oxidation resistance activity. We further demonstrate that induction of NCOA7-AS by IFN is dependent on IFN-receptor activation, the Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, and a canonical IFN-stimulated response element regulatory sequence upstream of exon 10a. We describe a new role for IFN-βs involving a mechanism of action that leads to an increase in resistance to inflammation-mediated oxidative stress.
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A striking (>60-fold) and robust induction of NCOA7-B occurs in peripheral blood mononuclear cells and macrophages treated with interferon-β-1b (IFNβ1b) or LPS.
“A striking (>60-fold) and robust induction of NCOA7-B occurs in peripheral blood mononuclear cells and macrophages treated with interferon-β-1b (IFNβ1b) or LPS.”
From ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease (2020) · cites this paper as [190]
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- Authors
- Yu, L., Croze, E., Yamaguchi, K. D., Tran, T., Reder, A. T., Litvak, V., & Volkert, M. R.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Bayer HealthCare Pharmaceuticals
- University of California, Los Angeles (US)
- University of Chicago (US)
- Corresponding author
- Volkert, Michael R.
- Venue
- Journal of Interferon & Cytokine Research
- Publisher
- SAGE Publications
- Published
- 2015-03
- Volume
- 35
- Issue
- 3
- Pages
- 186-199
- ISSN
- 1079-9907 (ISSN-L)
- 1557-7465
- PMC
- PMC4350146
- OpenAlex
- W2084761243
- Cited by
- 41
- References
- 64
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 1 · 2021: 6 · 2020: 8 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 3
- FWCI
- 1.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Interferon & Cytokine Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Teva Pharmaceutical Industries
- Cleveland Clinic
- Veracyte
- Bayer HealthCare
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- interferon beta-1b, aldo-keto reductase, JAK/STAT signaling, IFN-stimulated response element, oxidative stress resistance, multiple sclerosis, peripheral blood mononuclear cells
- MeSH terms
- Amino Acid Sequence, Cell Line, Humans, Immunotherapy, Leukocytes, Mononuclear, Molecular Sequence Data, Multiple Sclerosis, Oxidation-Reduction, Signal Transduction, Interferon-beta, Protein Structure, Tertiary, Receptors, Interferon, Oxidative Stress, Protein Isoforms, Regulatory Elements, Transcriptional, STAT Transcription Factors, Janus Kinases, Nuclear Receptor Coactivators
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