ArticleProceedings of the National Academy of Sciences of the United States of America1997
Activation of hypoxia-inducible factor 1alpha: posttranscriptional regulation and conformational change by recruitment of the Arnt transcription factor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 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
138 citing papers in PubMed, 410 citations in OpenAlex.
- Tissue-specific regulation of PNPLA3 promotes lipid remodeling in response to dietary and environmental challenges.Journal of hepatology · 2026Article
- A Perturb-seq screen guided by species divergence uncovers pathways for collateral artery formation.bioRxiv : the preprint server for biology · 2026Article
- Functional segregation of HIF-1α and AhR controls NK cell responsiveness under hypoxia.iScience · 2026Article
- The role of hypoxia-inducible factor-1α on colon cancer progression and metastasis.International journal of clinical oncology · 2025Review
- The Role of Gap Junctions in MSC-EA.hy926 (An Endothelial Cell Model) Crosstalk Under Hypoxic Stress: Regulation of the Angiogenic Response.International journal of molecular sciences · 2025Article
- Tissue-specific regulation of PNPLA3 promotes lipid remodeling in response to dietary and temperature stress.bioRxiv : the preprint server for biology · 2025Article
- A unique mechanism involving cocatalysis of enzyme and nonenzyme to form β-carboline and spirotryprostatins inScience advances · 2025Article
- Review
- TNFAIP2 promotes HIF1α transcription and breast cancer angiogenesis by activating the Rac1-ERK-AP1 signaling axis.Cell death & disease · 2024Article
- Detrimental interactions of hypoxia and complement MASP-1 in endothelial cells as a model for atherosclerosis-related diseases.Scientific reports · 2024Article
- Intersections of Fibrodysplasia Ossificans Progressiva and Traumatic Heterotopic Ossification.Biomolecules · 2024Review
- Achaete-scute family bHLH transcription factor 2 activation promotes hepatoblastoma progression.Cancer science · 2024Article
- Surviving winter on the Qinghai-Xizang Plateau: Extensive reversible protein phosphorylation plays a dominant role in regulating hypometabolism in hibernatingZoological research · 2024Article
- Glucose Deprivation Promotes Pseudohypoxia and Dedifferentiation in Lung Adenocarcinoma.Cancer research · 2024Article
- Nanotoxicity of multifunctional stoichiometric cobalt oxide nanoparticles (SCoONPs) with repercussions toward apoptosis, necrosis, and cancer necrosis factor (TNF-α) at nano-biointerfaces.Toxicology research · 2023Review
- Thrombotic Alterations under Perinatal Hypoxic Conditions: HIF and Other Hypoxic Markers.International journal of molecular sciences · 2023Review
- Angiogenesis and Hepatocellular Carcinoma: From Molecular Mechanisms to Systemic Therapies.Medicina (Kaunas, Lithuania) · 2023Review
- Adipose-Derived Stem Cells Improve Angiogenesis and Lymphangiogenesis in a Hypoxic Dermal Regeneration Model In Vitro.Medicina (Kaunas, Lithuania) · 2023Article
- The Role of Hypoxia in Brain Tumor Immune Responses.Brain tumor research and treatment · 2023Review
- Hypoxia-Inducible Factor-1: A Novel Therapeutic Target for the Management of Cancer, Drug Resistance, and Cancer-Related Pain.Cancers · 2022Review
78 more citing papers are in PubMed but not listed here.
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 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In response to hypoxia the hypoxia-inducible factor-1 (HIF-1) mediates transcriptional activation of a network of genes encoding erythropoietin, vascular endothelial growth factor, and several glycolytic enzymes. HIF-1 consists of a heterodimer of two basic helix-loop-helix PAS (Per/Arnt/Sim) proteins, HIF-1alpha and Arnt. HIF-1alpha and Arnt mRNAs are constitutively expressed and were not altered upon exposure of HeLa or HepG2 cells to hypoxia, suggesting that the activity of the HIF-1alpha-Arnt complex may be regulated by some as yet unknown posttranscriptional mechanism. In support of this model, we demonstrate here that Arnt protein levels were not increased under conditions that induce an hypoxic response in HeLa and HepG2 cells. However, under identical conditions, HIF-1alpha protein levels were rapidly and dramatically up-regulated, as assessed by immunoblot analysis. In addition, HIF-1alpha acquired a new conformational state upon dimerization with Arnt, rendering HIF-1alpha more resistant to proteolytic digestion in vitro. Dimerization as such was not sufficient to elicit the conformational change in HIF-1alpha, since truncated forms of Arnt that are capable of dimerizing with HIF-1alpha did not induce this effect. Moreover, the high affinity DNA binding form of the HIF-1alpha-Arnt complex was only generated by forms of Arnt capable of eliciting the allosteric change in conformation. In conclusion, the combination of enhanced protein levels and allosteric change by dimerization defines a novel mechanism for modulation of transcription factor activity.
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.