ArticleNature2015
Structural integration in hypoxia-inducible factors.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 205 papers.
What it found
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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.
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Who cites it
205 citing papers in PubMed.
- The role of hypoxia-inducible factors in myocardial ischaemia-reperfusion injury and cardioprotection.Nature reviews. Cardiology · 2026Review
- Juvenile hormone receptor relies on conserved domain interfaces for dimerization-dependent activity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- HIFs: The central drivers of tumors and their role as molecular switches in targeted therapy?Acta pharmaceutica Sinica. B · 2026Review
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- The clinical landscape of HIF2α inhibitors in oncology.Nature reviews. Clinical oncology · 2026Review
- The CLOCK-BMAL1 complex in circadian regulation: structure, mechanisms, and therapeutic targeting.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Weak Phd2-Hif-1α Affinity Coupled with High Basal Expression Is Predicted to Enhance HIF Pathway Flexibility in Nile Tilapia (Animals : an open access journal from MDPI · 2026Article
- Hypoxia-inducible factor-1α: Dual roles in maintaining neuronal homeostasis and neuronal degeneration via regulation of oxidative stress, mitochondrial dynamics, and bioenergetics.Journal of physiology and biochemistry · 2026Review
- Context-dependent variability of HIF heterodimers influences interactions with macromolecular and small molecule partners.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeting conserved domains of hypoxia-inducible factors for cancer therapy.The Journal of experimental medicine · 2026Article
- Integrated Molecular Docking and Network-Based Analysis Reveals Multitarget Interaction Patterns of Nutraceutical Compounds in Intervertebral Disc Degeneration.Biomedicines · 2026Article
- Conserved structural motifs in PAS, LOV, and CRY proteins regulate circadian rhythms and are therapeutic targets.FEBS letters · 2026Review
- Integration of circadian and hypoxia signaling via non-canonical heterodimerization.FEBS letters · 2026Review
- HIF-1α and BMAL1 in bone regeneration: crosstalk between hypoxia response and circadian rhythm.Bone research · 2026Review
- Discovery and characterization of a novel HIF-2α agonist for the treatment of CKD-related renal anemia.Acta pharmacologica Sinica · 2026Article
- Review
- The aryl hydrocarbon receptor: structure, signaling, physiology and pathology.Signal transduction and targeted therapy · 2026Review
- Targeting and dissociating HIF2α from the molecular chaperone Hsp70 triggers apoptosis in kidney cancer.Communications medicine · 2026Article
- Multimodal bHLH-PAS DNA binding controls specificity and drives obesity.Nucleic acids research · 2026Article
- The Inflammatory Milieu Exacerbates Anemia of Chronic Kidney Disease: From the Gut-Kidney Axis to Bone Marrow Hematopoiesis Inhibition.Kidney & blood pressure research · 2026Review
145 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hypoxia-inducible factors (HIFs) coordinate cellular adaptations to low oxygen stress by regulating transcriptional programs in erythropoiesis, angiogenesis and metabolism. These programs promote the growth and progression of many tumours, making HIFs attractive anticancer targets. Transcriptionally active HIFs consist of HIF-α and ARNT (also called HIF-1β) subunits. Here we describe crystal structures for each of mouse HIF-2α-ARNT and HIF-1α-ARNT heterodimers in states that include bound small molecules and their hypoxia response element. A highly integrated quaternary architecture is shared by HIF-2α-ARNT and HIF-1α-ARNT, wherein ARNT spirals around the outside of each HIF-α subunit. Five distinct pockets are observed that permit small-molecule binding, including PAS domain encapsulated sites and an interfacial cavity formed through subunit heterodimerization. The DNA-reading head rotates, extends and cooperates with a distal PAS domain to bind hypoxia response elements. HIF-α mutations linked to human cancers map to sensitive sites that establish DNA binding and the stability of PAS domains and pockets.
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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.