The DOI matches its Crossref record; 47 of the 48 references it cites were found in a registry or an index.
Hypoxia inducible factor 1α regulates T cell receptor signal transduction
Open accessAbstract
Low oxygen pressures exist in many solid tissues, including primary and secondary lymphoid organs. One key element in cellular adaptation to hypoxia is induced expression of hypoxia inducible factor (Hif) 1α. Here, we have examined the effect of Hif-1α, isolated from the myriad other effects of hypoxia, on T cell receptor (TCR) signaling in thymocytes. Because pVHL (von Hippel–Lindau protein) directs the proteolysis of Hif-1α under “normoxic” conditions, we achieved constitutive stabilization of Hif-1α through thymic deletion of Vhlh and reversed Hif-1α stabilization with double deletion of Vhlh and Hif-1 α. We found that constitutive activity of Hif-1α resulted in diminished Ca 2+ response upon TCR crosslinking despite equivalent activation of phospholipase C γ1 , normal intracellular Ca 2+ stores, and normal entry of Ca 2+ across the plasma membrane. Altered Ca 2+ response was instead due to accelerated removal of Ca 2+ from the cytoplasm into intracellular compartments, which occurred in association with Hif-1α-dependent overexpression of the calcium pump SERCA2 (sarcoplasmic/endoplasmic reticulum calcium ATPase 2). These data suggest a unique mechanism for control of TCR signaling through Hif-1α, which may be operative at the physiologic oxygen tensions seen in solid lymphoid organs.
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“Constitutive activation of Hif-1α in Vhl-deficient thymocytes also resulted in a reduced calcium response following TCR cross-linking that resulted from increased removal of calcium from the cytoplasm via Hif-1α-induced increases in SERCA2 calcium pumps [92].”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [92]
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The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
Close Contacts with the Endoplasmic Reticulum as Determinants of Mitochondrial Ca 2+ Responses
Rizzuto, R., Pinton, P., Carrington, W., Fay, F. S., Fogarty, K. E., Lifshitz, L. M., Tuft, R. A., & Pozzan, T. (1998) · Science · doi:10.1126/science.280.5370.1763 · Cited by 2,257
Huang, L. E., Gu, J., Schau, M., & Bunn, H. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.7987 · Cited by 2,113
Oxygen sensing by HIF hydroxylases
Schofield, C. J., & Ratcliffe, P. J. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1366 · Cited by 2,068
HIF-1α is essential for myeloid cell-mediated inflammation
Cramer, T., Yamanishi, Y., Clausen, B. E., Förster, I., Pawlinski, R., Mackman, N., Haase, V. H., Jaenisch, R., Corr, M., Nizet, V., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00154-5 · Cited by 2,046
Self-citationCalcium oscillations increase the efficiency and specificity of gene expression
Dolmetsch, R. E., Xu, K., & Lewis, R. S. (1998) · Nature · doi:10.1038/31960 · Cited by 1,896
Smiley, S. T., Reers, M., Mottola-Hartshorn, C., Lin, M., Chen, A. B., Smith, T. W., Steele, G., & Chen, L. B. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.9.3671 · Cited by 1,629
A Critical Role for Dnmt1 and DNA Methylation in T Cell Development, Function, and Survival
Lee, P. P., Fitzpatrick, D. R., Beard, C., Jessup, H. K., Lehar, S. M., Makar, K. W., Pérez‐Melgosa, M., Sweetser, M. T., Schlissel, M. S., Nguyen, S., et al. (2001) · Immunity · doi:10.1016/s1074-7613(01)00227-8 · Cited by 1,282
HIF-1 and mechanisms of hypoxia sensing
Semenza, G. L. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00194-0 · Cited by 1,267
Laughner, E., Taghavi, P., Chiles, K., Mahon, P. C., & Semenza, G. L. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.12.3995-4004.2001 · Cited by 1,256
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- Braun, R. D., Lanzen, J. L., Snyder, S. A. & Dewhirst, M. W. (2001) Am. J. Physiol. 280, H2533-H2544.
- Ryan, H. E., Poloni, M., McNulty, W., Elson, D., Gassmann, M., Arbeit, J. M. & Johnson, R. S. (2000) Cancer Res. 60, 4010-4015.10945599
- Jiang, B. H., Jiang, G., Zheng, J. Z., Lu, Z., Hunter, T. & Vogt, P. K. (2001) Cell Growth Differ. 12, 363-369.11457733
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The lymphocyte in inflammatory angiogenesis
Paleolog, E. M., & Akhavani, M. (2008) · Birkhäuser Basel eBooks · doi:10.1007/978-3-7643-7650-5_4
T cells and smoke-induced airway inflammation
Mikko, M. (2010) · Figshare
Erekul, K. B. (2008) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-7217
Understanding CD8 T cell function under the tumour environment condition hypoxia
Townsend, K. N. (2012) · UVic’s Research and Learning Repository (University of Victoria)
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Metadata
- Authors
- Neumann, A. K., Yang, J., Biju, M. P., Joseph, S. K., Johnson, R. S., Haase, V. H., Freedman, B. D., & Turka, L. A.
- Affiliations
- Thomas Jefferson University (US)
- Department of Medicine and Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104; Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107; Division of Biological Sciences, University of California, San Diego, CA 92093; and Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-11-14
- Volume
- 102
- Issue
- 47
- Pages
- 17071-17076
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1287984
- OpenAlex
- W2071062200
- Cited by
- 120
- References
- 48
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 6 · 2020: 7 · 2019: 4 · 2018: 7 · 2017: 3 · 2016: 7 · 2015: 4 · 2014: 5 · 2013: 5 · 2012: 7
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health
- National Cancer Institute (R01CA100787)
- National Institute of Allergy and Infectious Diseases (AI 43626, R01AI043626, R21AI043626, R01AI060921)
- 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 › Signaling Pathways in Disease
- Keywords
- hypoxia-inducible factor-1α, T cell receptor signaling, thymocytes, calcium signaling, von Hippel-Lindau protein, HIF-1α stabilization, SERCA2, calcium pump, phospholipase C-gamma1, hypoxia
- MeSH terms
- Calcium-Transporting ATPases, Animals, Mice, Inbred BALB C, Mice, Inbred C57BL, Mitochondria, Receptors, Antigen, T-Cell, Thymus Gland, Down-Regulation, Mice, Knockout, Calcium Signaling, Mice, Von Hippel-Lindau Tumor Suppressor Protein, Hypoxia-Inducible Factor 1, alpha Subunit, Sarcoplasmic Reticulum Calcium-Transporting ATPases
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