Preferential expression of the novel alternative isoform I.3 of hypoxia-inducible factor 1α in activated human T lymphocytes
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Hypoxia-inducible factor-1alpha (HIF-1alpha) is critical not only in the regulation of oxygen homeostasis but also in the regulation of innate and adaptive immune systems. We previously reported that T-cell receptor-mediated activation of T cells in mice leads to the expression of an alternative isoform of HIF-1alpha that inhibits activated T cells in a delayed negative feed-back manner. In this paper, we describe a novel mRNA isoform of human HIF-1alpha that is upregulated in peripheral T lymphocytes after T-cell receptor stimulation. This activation- inducible isoform is expressed using the alternative first exon I.3, and it encodes a protein that is 24 amino acids longer than the ubiquitous HIF-1alpha isoform. This mRNA isoform I.3 of HIF-1alpha is expressed in a tissue-specific manner with the highest expression found in peripheral blood leukocytes and the thymus.
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TCR activation can induce expression of distinct splice isoforms of Hif-1α mRNA in human and mouse T cells.
“TCR activation can also induce expression of distinct splice isoforms of Hif-1α mRNA in human and mouse T cells, although the unique contribution of these splice isoforms to gene regulation remains unclear [8, 70].”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [70]
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- Authors
- Lukashev, D., & Sitkovsky, M.
- Affiliations
- Northeastern University (US)
- Corresponding author
- Lukashev, Dmitriy
- ORCID
- Sitkovsky, Michail
- Venue
- Human Immunology
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 69
- Issue
- 7
- Pages
- 421-425
- ISSN
- 0198-8859 (ISSN-L)
- PMC
- PMC2577919
- OpenAlex
- W2036353955
- Cited by
- 25
- References
- 16
- Citations by year
- 2026: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2016: 3 · 2014: 3 · 2013: 2 · 2012: 4
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA112561)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- hypoxia-inducible factor-1α, alternative splicing, T cell activation, T cell receptor stimulation, peripheral blood leukocytes, thymus, tissue-specific gene expression, oxygen homeostasis, immune regulation
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Cloning, Molecular, Exons, HeLa Cells, Humans, Lymphocyte Activation, Molecular Sequence Data, Organ Specificity, RNA, Messenger, T-Lymphocytes, Up-Regulation, Gene Expression, Alternative Splicing, Protein Isoforms, Mice, Hypoxia-Inducible Factor 1, alpha Subunit
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