ArticleMolecular cell2008
Small-molecule inhibitors of HIF-2a translation link its 5'UTR iron-responsive element to oxygen sensing.
Article in Molecular cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
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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.
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Who cites it
110 citing papers in PubMed, 188 citations in OpenAlex.
- Iron Prevents Hypoxia-Associated Inflammation Through the Regulation of Nuclear Factor-κB in the Intestinal Epithelium.Cellular and molecular gastroenterology and hepatology · 2019Trial
- Elevation of iron storage in humans attenuates the pulmonary vascular response to hypoxia.Journal of applied physiology (Bethesda, Md. : 1985) · 2016Trial
- Article
- The clinical landscape of HIF2α inhibitors in oncology.Nature reviews. Clinical oncology · 2026Review
- Iron and the lung: emerging roles of iron metabolism in pulmonary disease pathogenesis and therapy.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Genome-wide CRISPR screen identifies a cytokine-enhancer circuit driving HIF-2α activation in renal cancer.The Journal of clinical investigation · 2026Article
- Low Wall Shear Stress Promotes Atheroma via Arterial Iron Accumulation.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- The HIF axes in cancer: angiogenesis, metabolism, and immune-modulation.Trends in biochemical sciences · 2025Review
- Glucose deprivation impairs hypoxia-inducible factor-1α synthesis.Discover oncology · 2024Article
- NADPH Oxidase 4: Crucial for Endothelial Function under Hypoxia-Complementing Prostacyclin.Antioxidants (Basel, Switzerland) · 2024Article
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Microbiota-assisted iron uptake promotes immune tolerance in the intestine.Nature communications · 2023Article
- Article
- Updated perspective of EPAS1 and the role in pulmonary hypertension.Frontiers in cell and developmental biology · 2023Review
- ISCA2 inhibition decreases HIF and induces ferroptosis in clear cell renal carcinoma.Oncogene · 2022Article
- Mitochondrial Regulation of the Hypoxia-Inducible Factor in the Development of Pulmonary Hypertension.Journal of clinical medicine · 2022Review
- Targeting HIF-2α in the Tumor Microenvironment: Redefining the Role of HIF-2α for Solid Cancer Therapy.Cancers · 2022Review
- Host and microbiota derived extracellular vesicles: Crucial players in iron homeostasis.Frontiers in medicine · 2022Review
- Dysregulation of the sensory and regulatory pathways controlling cellular iron metabolism in unilateral obstructive nephropathy.American journal of physiology. Renal physiology · 2022Article
- Loss of Endothelial Hypoxia Inducible Factor-Prolyl Hydroxylase 2 Induces Cardiac Hypertrophy and Fibrosis.Journal of the American Heart Association · 2021Article
50 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Cells transiently adapt to hypoxia by globally decreasing protein translation. However, specific proteins needed to respond to hypoxia evade this translational repression. The mechanisms of this phenomenon remain unclear. We screened for and identified small molecules that selectively decrease HIF-2a translation in an mTOR-independent manner, by enhancing the binding of Iron-Regulatory Protein 1 (IRP1) to a recently reported iron-responsive element (IRE) within the 5'-untranslated region (UTR) of the HIF-2a message. Knocking down the expression of IRP1 by shRNA abolished the effect of the compounds. Hypoxia derepresses HIF-2a translation by disrupting the IRP1-HIF-2a IRE interaction. Thus, this chemical genetic analysis describes a molecular mechanism by which translation of the HIF-2a message is maintained during conditions of cellular hypoxia through inhibition of IRP-1-dependent repression. It also provides the chemical tools for studying this phenomenon.
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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.