ArticleThe Biochemical journal2002
A dominant-negative isoform lacking exons 11 and 12 of the human hypoxia-inducible factor-1alpha gene.
Article in The Biochemical journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 73 citations in OpenAlex.
- Interaction of pregnane X receptor with hypoxia-inducible factor-1 regulates chemoresistance of prostate cancer cells.Cancer drug resistance (Alhambra, Calif.) · 2023Article
- The Relationship Between the Tumor Cell Expression of Hypoxic Markers and Survival in Patients With ER-positive Invasive Ductal Breast Cancer.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2022Article
- Action Sites and Clinical Application of HIF-1α Inhibitors.Molecules (Basel, Switzerland) · 2022Review
- Macrophage Motility in Wound Healing Is Regulated by HIF-1α via S1P Signaling.International journal of molecular sciences · 2021Review
- Human Red Blood Cells Modulate Cytokine Expression in Monocytes/Macrophages Under Anoxic Conditions.Frontiers in physiology · 2021Article
- Subcellular Localization Signals of bHLH-PAS Proteins: Their Significance, Current State of Knowledge and Future Perspectives.International journal of molecular sciences · 2019Review
- Aberrant expression of alternative isoforms of transcription factors in hepatocellular carcinoma.World journal of hepatology · 2018Review
- A hypoxia-inducible factor 1α null splice variant lacking exon 10.Cell death & disease · 2017Article
- Hypoxia-response element (HRE)-directed transcriptional regulation of the rat lysyl oxidase gene in response to cobalt and cadmium.Toxicological sciences : an official journal of the Society of Toxicology · 2013Article
- Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2.Physiological reviews · 2012Review
- Hypoxia-inducible factor (HIF1α) gene expression in human shock states.Critical care (London, England) · 2012Article
- The effect of antioxidants on the production of pro-inflammatory cytokines and orthodontic tooth movement.Molecules and cells · 2011Article
- Hypoxia inducible factor-1α directly induces the expression of receptor activator of nuclear factor-κB ligand in periodontal ligament fibroblasts.Molecules and cells · 2011Article
- Hypoxia-inducible factor α subunit stabilization by NEDD8 conjugation is reactive oxygen species-dependent.The Journal of biological chemistry · 2011Article
- HIF1alpha isoforms in benign and malignant prostate tissue and their correlation to neuroendocrine differentiation.BMC cancer · 2010Article
- Hypoxia inducible factor 1alpha gene (HIF-1alpha) splice variants: potential prognostic biomarkers in breast cancer.BMC medicine · 2010Article
- Brain tumor hypoxia: tumorigenesis, angiogenesis, imaging, pseudoprogression, and as a therapeutic target.Journal of neuro-oncology · 2009Review
- Prognostic significance of Hypoxia-Inducible Factor 1 alpha(HIF-1 alpha) expression in serous ovarian cancer: an immunohistochemical study.BMC cancer · 2008Article
- Regulation of gene expression by hypoxia: integration of the HIF-transduced hypoxic signal at the hypoxia-responsive element.Clinica chimica acta; international journal of clinical chemistry · 2008Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible factor-1alpha (HIF-1alpha), a member of the transcription family characterized by a basic helix-loop-helix (bHLH) domain and a PAS domain, regulates the transcription of hypoxia-inducible genes involved in erythropoiesis, vascular remodelling and glucose/energy metabolism. It contains bHLH/PAS domains in the N-terminal half, and a nuclear localization signal (NLS) and two transactivation domains (TADs) in the C-terminal half. It also has an oxygen-dependent degradation (ODD) domain, which is required to degrade HIF-1alpha protein by the ubiquitin-proteasome pathway. In this study, we identified a new alternatively spliced variant of human HIF-1alpha mRNA, which lacked both exons 11 and 12, producing a frame shift and giving a shorter form of HIF-1alpha. In the corresponding protein, a part of the ODD domain, both TADs and the C-terminal NLS motif were missing. Expression of endogenous HIF-1alpha variant protein was identified using immunoprecipitation and immunoblotting methods. The expressed HIF-1alpha variant exhibited neither the activity of transactivation nor hypoxia-induced nuclear translocation. In contrast with HIF-1alpha, the variant was strikingly stable in normoxic conditions and not up-regulated to such an extent by hypoxia, cobalt ions or desferrioxamine. It was also demonstrated that the HIF-1alpha variant competed with endogenous HIF-1alpha and suppressed HIF-1 activity, resulting in the down-regulation of mRNA expression of hypoxia-inducible genes. The association of the variant and arylhydrocarbon receptor nuclear translocator in the cytoplasm may be related to the inhibition of HIF-1 activity. It is assumed that this isoform preserves the balance between aerobic and anaerobic metabolism by counteracting the overaction of HIF-1alpha.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.