The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
Human HIF‐3α4 is a dominant‐negative regulator of HIF‐1 and is down‐regulated in renal cell carcinoma
Abstract
A universal response to changes in cellular oxygen tension is governed by a family of heterodimeric transcription factors called hypoxia‐inducible factor (HIF). Tumor hypoxia, as well as various cancer‐causing mutations, has been shown to elevate the level of HIF‐1α, signifying a critical role of the HIF pathway in cancer development. The recently identified third member of the human HIF‐α family, HIF‐3α, produces multiple splice variants that contain extra DNA binding elements and protein‐protein interaction motifs not found in HIF‐1α or HIF‐2α. Here we report the molecular cloning of the alternatively spliced human HIF‐3α variant HIF‐3α4 and show that it attenuates the ability of HIF‐1 to bind hypoxia‐responsive elements located within the enhancer/promoter of HIF target genes. The overexpression of HIF‐3α4 suppresses the transcriptional activity of HIF‐1 and siRNAmediated knockdown of the endogenous HIF‐3α4 increases transcription by hypoxia‐inducible genes. HIF‐3α4 itself is oxygen‐regulated, suggesting a novel feedback mechanism of controlling HIF‐1 activity. Furthermore, the expression of HIF‐3α4 is dramatically down‐regulated in the majority of primary renal carcinomas. These results demonstrate an important dominant‐negative regulation of HIF‐1‐mediated gene transcription by HIF‐3α4 in vivo and underscore its potential significance in renal epithelial oncogenesis. Maynard, M. A., Evans, A. J., Hosomi, T., Hara, S., Jewett, M. A. S., Ohh, M. Human HIF‐3α4 is a dominant‐negative regulator of HIF‐1 and is down‐regulated in renal cell carcinoma. FASEB J. 19, 1396–1406 (2005)
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase
Selak, M. A., Armour, S. M., MacKenzie, E. D., Boulahbel, H., Watson, D. G., Mansfield, K. D., Pan, Y., Simon, M. C., Thompson, C. B., & Gottlieb, E. (2005) · Cancer Cell · doi:10.1016/j.ccr.2004.11.022 · Cited by 2,108
Regulation of Mammalian O 2 Homeostasis by Hypoxia-Inducible Factor 1
Semenza, G. L. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.551 · Cited by 1,914 · cited 1×
“The transactivation property of HIF is in concert with the binding of transcriptional coactivators such as p300/ CBP to CAD of HIF- ( 1-3 ).”
BackgroundOhh, M., Park, C. W., Ivan, M., Hoffman, M. A., Kim, T.-Y., Huang, L. E., Pavletich, N., Chau, V., & Kaelin, W. G. (2000) · Nature Cell Biology · doi:10.1038/35017054 · Cited by 1,577
Self-citationLaughner, 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 · cited 1×
“For example, loss of p53 in various tumors or increased expression of HER2 receptor tyrosine kinase in breast cancer enhances HIF-1 expression and intensifies HIF-1-dependent transcription, often correlating with tumor aggressiveness (9, 10 ).”
BackgroundDimerization, DNA Binding, and Transactivation Properties of Hypoxia-inducible Factor 1
Jiang, B.-H., Rue, E., Wang, G. L., Roe, R., & Semenza, G. L. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.30.17771 · Cited by 1,106 · cited 2×
“required for heterodimerization and DNA binding (4).”
BackgroundRegulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1α
Ravi, R., Mookerjee, B., Bhujwalla, Z. M., Sutter, C. H., Artemov, D., Zeng, Q., Dillehay, L. E., Madan, A., Semenza, G. L., & Bedi, A. (2000) · Genes & Development · doi:10.1101/gad.14.1.34 · Cited by 967
Loss of PTEN facilitates HIF-1-mediated gene expression
Zundel, W., Schindler, C., Haas-Kogan, D., Koong, A., Kaper, F., Chen, E., Gottschalk, A. R., Ryan, H. E., Johnson, R. S., Jefferson, A. B., et al. (2000) · Genes & Development · doi:10.1101/gad.14.4.391 · Cited by 840
Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein
Kondo, K., Klco, J., Nakamura, E., Lechpammer, M., & Kaelin, W. G. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00043-0 · Cited by 761
Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression
Makino, Y., Cao, R., Svensson, K., Bertilsson, G., Asman, M., Tanaka, H., Cao, Y., Berkenstam, A., & Poellinger, L. (2001) · Nature · doi:10.1038/35107085 · Cited by 705
Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia
Ang, S. O., Chen, H., Hirota, K., Gordeuk, V. R., Jelinek, J., Guan, Y., Liu, E., Sergueeva, A. I., Miasnikova, G. Y., Mole, D., et al. (2002) · Nature Genetics · doi:10.1038/ng1019 · Cited by 510
Cited by
Grubman, A., Chew, G., Ouyang, J. F., Sun, G., Choo, X. Y., McLean, C., Simmons, R. K., Buckberry, S., Vargas-Landin, D. B., Poppe, D., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0539-4 · Cited by 956
Elvidge, G. P., Glenny, L., Appelhoff, R. J., Ratcliffe, P. J., Ragoussis, J., & Gleadle, J. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m511408200 · Cited by 464
The von Hippel-Lindau Tumor Suppressor Protein and Clear Cell Renal Carcinoma
Kaelin, W. G. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-1865 · Cited by 336
miRNAs regulate the HIF switch during hypoxia: a novel therapeutic target
Serocki, M., Bartoszewska, S., Janaszak-Jasiecka, A., Ochocka, R. J., Collawn, J. F., & Bartoszewski, R. (2018) · Angiogenesis · doi:10.1007/s10456-018-9600-2 · Cited by 288
Hypoxia-inducible factor 3 biology: complexities and emerging themes
Duan, C. (2016) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00315.2015 · Cited by 269
Metadata
- Authors
- Maynard, M. A., Evans, A. J., Hosomi, T., Hara, S., Jewett, M. A. S., & Ohh, M.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2005-09
- Volume
- 19
- Issue
- 11
- Pages
- 1396-1406
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2102365921
- Cited by
- 193
- References
- 13
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- closed
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Human HIF‐3α4 is a dominant‐negative regulator of HIF‐1 and is down‐regulated in renal cell carcinoma. https://app.cochat.ai/papers/10.1096/fj.05-3788com
- The paper
- Maynard, M. A., Evans, A. J., Hosomi, T., Hara, S., Jewett, M. A. S., & Ohh, M. (2005). Human HIF‐3α4 is a dominant‐negative regulator of HIF‐1 and is down‐regulated in renal cell carcinoma. The FASEB Journal. https://doi.org/10.1096/fj.05-3788com
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
