ArticleNature communications2019
Evolution of metazoan oxygen-sensing involved a conserved divergence of VHL affinity for HIF1α and HIF2α.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Redox regulation: mechanisms, biology and therapeutic targets in diseases.Signal transduction and targeted therapy · 2025Review
- The p-MYH9/USP22/HIF-1α axis promotes lenvatinib resistance and cancer stemness in hepatocellular carcinoma.Signal transduction and targeted therapy · 2024Article
- Cathepsins L and B target HIF1α for oxygen-independent proteolytic cleavage.Scientific reports · 2024Article
- Structural basis for binding of the renal carcinoma target hypoxia-inducible factor 2α to prolyl hydroxylase domain 2.Proteins · 2023Article
- Genomic analysis of hypoxia inducible factor alpha in ray-finned fishes reveals missing Ohnologs and evidence of widespread positive selection.Scientific reports · 2022Article
- The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies.Molecular cancer · 2022Review
- Origin and evolution of animal multicellularity in the light of phylogenomics and cancer genetics.Medical oncology (Northwood, London, England) · 2022Article
- The origin and distribution of the main oxygen sensing mechanism across metazoans.Frontiers in physiology · 2022Article
- Analysis of Multiplicity of Hypoxia-Inducible Factors in the Evolution ofFrontiers in genetics · 2020Article
- High Expression of Succinate Dehydrogenase Subunit A Which Is Regulated by Histone Acetylation, Acts as a Good Prognostic Factor of Multiple Myeloma Patients.Frontiers in oncology · 2020Article
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3 authors.
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Abstract
Duplication of ancestral hypoxia-inducible factor (HIF)α coincided with the evolution of vertebrate species. Paralogs HIF1α and HIF2α are the most well-known factors for modulating the cellular transcriptional profile following hypoxia. However, how the processes of natural selection acted upon the coding region of these two genes to optimize the cellular response to hypoxia during evolution remains unclear. A key negative regulator of HIFα is von Hippel-Lindau (VHL) tumour suppressor protein. Here we show that evolutionarily-relevant substitutions can modulate a secondary contact between HIF1α Met561 and VHL Phe91. Notably, HIF1α binds more tightly than HIF2α to VHL due to a conserved Met to Thr substitution observed in the vertebrate lineage. Similarly, substitution of VHL Phe91 with Tyr, as seen in invertebrate species, decreases VHL affinity for both HIF1α and HIF2α. We propose that vertebrate evolution involved a more complex hypoxia response with fine-tuned divergence of VHL affinity for HIF1α and HIF2α.
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