ArticleThe EMBO journal1999
Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300.
Article in The EMBO journal, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 193 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
193 citing papers in PubMed, 585 citations in OpenAlex.
- Computational Drug Repurposing for Alzheimer's Disease via Sheaf Theoretic Population-Scale Analysis of snRNA-Seq Data.Journal of medicinal chemistry · 2026Article
- Article
- Decoding the Tumor Microenvironment: Insights and New Targets from Single-Cell Sequencing and Spatial Transcriptomics.Current issues in molecular biology · 2025Review
- Are Hippocampal Hypoperfusion and ATP Depletion Prime Movers in the Genesis of Alzheimer's Disease? A Review of Recent Pertinent Observations from Molecular Biology.International journal of molecular sciences · 2025Review
- Review
- Revisiting the role of hypoxia-inducible factors and nuclear factor erythroid 2-related factor 2 in regulating macrophage inflammation and metabolism.Frontiers in cellular and infection microbiology · 2024Review
- Peroxiredoxins in erythrocytes: far beyond the antioxidant role.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Evolutionarily Conserved Role of Thioredoxin Systems in Determining Longevity.Antioxidants (Basel, Switzerland) · 2023Review
- Pharmacological inhibition of the SKP2/p300 signaling axis restricts castration-resistant prostate cancer.Neoplasia (New York, N.Y.) · 2023Article
- Article
- Hypoxia-Inducible Factor-2alpha Affects the MEK/ERK Signaling Pathway via Primary Cilia in Connection with the Intraflagellar Transport Protein 88 Homolog.Molecular and cellular biology · 2023Article
- Cysteine Oxidation to Sulfenic Acid in APE1 Aids G-Quadruplex Binding While Compromising DNA Repair.ACS chemical biology · 2022Article
- Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles.World journal of stem cells · 2022Review
- Roles of Cullin-RING Ubiquitin Ligases in Cardiovascular Diseases.Biomolecules · 2022Review
- Targeting HIF-2α in the Tumor Microenvironment: Redefining the Role of HIF-2α for Solid Cancer Therapy.Cancers · 2022Review
- Non-canonical approaches to targeting hypoxic tumors.American journal of cancer research · 2022Review
- Regulation of PRKN-independent mitophagy.Autophagy · 2022Review
- Loss ofFrontiers in cellular and infection microbiology · 2022Article
- Oxygen-sensing mechanisms in development and tissue repair.Development (Cambridge, England) · 2021Review
- Changes in the Plasma Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1(APE1/Ref-1) Level during Cancer Surgery: An Observational Study.Medicina (Kaunas, Lithuania) · 2021Observational
133 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
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible factor 1 alpha (HIF1alpha) and its related factor, HLF, activate expression of a group of genes such as erythropoietin in response to low oxygen. Transfection analysis using fusion genes of GAL4DBD with various fragments of the two factors delineated two transcription activation domains which are inducible in response to hypoxia and are localized in the C-terminal half. Their sequences are conserved between HLF and HIF1alpha. One is designated NAD (N-terminal activation domain), while the other is CAD (C-terminal activation domain). Immunoblot analysis revealed that NADs, which were rarely detectable at normoxia, became stabilized and accumulated at hypoxia, whereas CADs were constitutively expressed. In the mammalian two-hybrid system, CAD and NAD baits enhanced the luciferase expression from a reporter gene by co-transfection with CREB-binding protein (CBP) prey, whereas CAD, but not NAD, enhanced beta-galactosidase expression in yeast by CBP co-expression, suggesting that NAD and CAD interact with CBP/p300 by a different mechanism. Co-transfection experiments revealed that expression of Ref-1 and thioredoxin further enhanced the luciferase activity expressed by CAD, but not by NAD. Amino acid replacement in the sequences of CADs revealed a specific cysteine to be essential for their hypoxia-inducible interaction with CBP. Nuclear translocation of thioredoxin from cytoplasm was observed upon reducing O2 concentrations.
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.