ArticleNature communications2022
Identification of oleoylethanolamide as an endogenous ligand for HIF-3α.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The trial behind it
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Exploration of tropocollagen unwinding by cathepsin K dimer with chondroitin 4-sulphate through microsecond timescale molecular dynamics.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Mitochondrial Transplantation Rejuvenates Aging Heart by Restoring Mitophagy Flux via the HIF-3α-BNIP3 Axis.Aging cell · 2026Article
- HIFs: The central drivers of tumors and their role as molecular switches in targeted therapy?Acta pharmaceutica Sinica. B · 2026Review
- Oleoylethanolamide enhances regulatory T Cell function to accelerate plaque regression in atherosclerosis via PPARα activation.The Journal of biological chemistry · 2026Article
- 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
- 1,2-propanediol ameliorated radiation-induced intestinal injury in mice.Scientific reports · 2026Article
- Sex-specific association between low oral doses of cannabidiol (CBD) and plasma concentration of anandamide (AEA), N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA) in healthy occasional cannabis users.Journal of cannabis research · 2026Article
- Review
- Molecular mechanism of the crosstalk between glucocorticoid receptor (GR) and hypoxia-inducible factor 3α (HIF-3α) pathways.Marine life science & technology · 2025Article
- HIF-3α Facilitates the Proliferation and Migration in Pancreatic Cancer by Inhibiting Autophagy Through Downregulating TP53INP2.Cell biochemistry and biophysics · 2025Article
- Pharmacological targeting of BMAL1 modulates circadian and immune pathways.Nature chemical biology · 2025Article
- Structural basis for the ligand-dependent activation of heterodimeric AHR-ARNT complex.Nature communications · 2025Article
- Regulation of gene expression through protein-metabolite interactions.npj metabolic health and disease · 2025Review
- RNA-seq analysis of blood from cave- and surface-dwellingFrontiers in physiology · 2025Article
- Pharmacological potential of endocannabinoid and endocannabinoid-like compounds in protecting intestinal structure and metabolism under high-fat conditions.Frontiers in pharmacology · 2025Review
- Gating residues govern ligand unbinding kinetics from the buried cavity in HIF-2α PAS-B.Protein science : a publication of the Protein Society · 2024Article
- Pilot Study on the Effect of Patient Condition and Clinical Parameters on Hypoxia-Induced Factor Expression:International journal of molecular sciences · 2024Article
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Platanosides from Platanus × acerifolia: New molecules, SAR, and target validation of a strong lead for drug-resistant bacterial infections and the associated sepsis.Bioorganic chemistry · 2024Article
- Per-ARNT-Sim (PAS) Domains in Basic Helix-Loop-Helix (bHLH)-PAS Transcription Factors and Coactivators: Structures and Mechanisms.Journal of molecular biology · 2024Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Hypoxia-inducible factors (HIFs) are α/β heterodimeric transcription factors modulating cellular responses to the low oxygen condition. Among three HIF-α isoforms, HIF-3α is the least studied to date. Here we show that oleoylethanolamide (OEA), a physiological lipid known to regulate food intake and metabolism, binds selectively to HIF-3α. Through crystallographic analysis of HIF-3 α/β heterodimer in both apo and OEA-bound forms, hydrogen-deuterium exchange mass spectrometry (HDX-MS), molecular dynamics (MD) simulations, and biochemical and cell-based assays, we unveil the molecular mechanism of OEA entry and binding to the PAS-B pocket of HIF-3α, and show that it leads to enhanced heterodimer stability and functional modulation of HIF-3. The identification of HIF-3α as a selective lipid sensor is consistent with recent human genetic findings linking HIF-3α with obesity, and demonstrates that endogenous metabolites can directly interact with HIF-α proteins to modulate their activities, potentially as a regulatory mechanism supplementary to the well-known oxygen-dependent HIF-α hydroxylation.
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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.