MYLIP attenuates hypoxia tolerance by inducing K27-linked polyubiquitination and subsequent proteasomal degradation of HIF-α.
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| Autori principali: | , , , , , , , , , , |
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| Natura: | Artículo científico |
| Lingua: | en |
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Communications biology
2025
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| _version_ | 1868266201710329856 |
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| author | Li, Jun Li, Zhi Li, Xiong Li, Ziyi Song, Yanan Yuan, Le Wang, Yanyi Yan, Runkun Lai, Fuxiang Wang, Jing Xiao, Wuhan |
| author_facet | Li, Jun Li, Zhi Li, Xiong Li, Ziyi Song, Yanan Yuan, Le Wang, Yanyi Yan, Runkun Lai, Fuxiang Wang, Jing Xiao, Wuhan Li, Jun Li, Zhi Li, Xiong Li, Ziyi Song, Yanan Yuan, Le Wang, Yanyi Yan, Runkun Lai, Fuxiang Wang, Jing Xiao, Wuhan |
| collection | PubMed - marine biology |
| contents | MYLIP attenuates hypoxia tolerance by inducing K27-linked polyubiquitination and subsequent proteasomal degradation of HIF-α. Li, Jun Li, Zhi Li, Xiong Li, Ziyi Song, Yanan Yuan, Le Wang, Yanyi Yan, Runkun Lai, Fuxiang Wang, Jing Xiao, Wuhan Animals Hypoxia-Inducible Factor 1, alpha Subunit Ubiquitination Proteasome Endopeptidase Complex Zebrafish Ubiquitin-Protein Ligases Mice Hypoxia Humans Basic Helix-Loop-Helix Proteins Proteolysis HEK293 Cells Signal Transduction Lysine Endothelial PAS Domain-Containing Protein 1 Hypoxia tolerance is mainly controlled by the hypoxia signaling pathway and HIF-1α/2α serve as master regulators in this pathway. Here we identify MYLIP, an E3 ubiquitin ligase thought to specifically target lipoprotein receptors, as a downstream target of HIF-2α and a negative regulator of both HIF-1α and HIF-2α. MYLIP interacts with HIF-1α/2α and catalyzes K27-linked polyubiquitination at lysine 118/442 (HIF-1α) or lysine 117 (HIF-2α). This modification induces proteasomal degradation of HIF-1α, resulting in inhibition of hypoxia signaling. Furthermore, Mylip-deficient bluntsnout bream, zebrafish and mice are more tolerant to hypoxia. These findings reveal a role for MYLIP in regulating hypoxia signaling and identify a target for the development of fish strains with high hypoxia tolerance for the benefit of the aquaculture industry. |
| format | Artículo científico |
| id | pubmed_40399570 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Communications biology |
| record_format | pubmed |
| spellingShingle | MYLIP attenuates hypoxia tolerance by inducing K27-linked polyubiquitination and subsequent proteasomal degradation of HIF-α. Li, Jun Li, Zhi Li, Xiong Li, Ziyi Song, Yanan Yuan, Le Wang, Yanyi Yan, Runkun Lai, Fuxiang Wang, Jing Xiao, Wuhan Animals Hypoxia-Inducible Factor 1, alpha Subunit Ubiquitination Proteasome Endopeptidase Complex Zebrafish Ubiquitin-Protein Ligases Mice Hypoxia Humans Basic Helix-Loop-Helix Proteins Proteolysis HEK293 Cells Signal Transduction Lysine Endothelial PAS Domain-Containing Protein 1 MYLIP attenuates hypoxia tolerance by inducing K27-linked polyubiquitination and subsequent proteasomal degradation of HIF-α. Li, Jun Li, Zhi Li, Xiong Li, Ziyi Song, Yanan Yuan, Le Wang, Yanyi Yan, Runkun Lai, Fuxiang Wang, Jing Xiao, Wuhan Animals Hypoxia-Inducible Factor 1, alpha Subunit Ubiquitination Proteasome Endopeptidase Complex Zebrafish Ubiquitin-Protein Ligases Mice Hypoxia Humans Basic Helix-Loop-Helix Proteins Proteolysis HEK293 Cells Signal Transduction Lysine Endothelial PAS Domain-Containing Protein 1 Hypoxia tolerance is mainly controlled by the hypoxia signaling pathway and HIF-1α/2α serve as master regulators in this pathway. Here we identify MYLIP, an E3 ubiquitin ligase thought to specifically target lipoprotein receptors, as a downstream target of HIF-2α and a negative regulator of both HIF-1α and HIF-2α. MYLIP interacts with HIF-1α/2α and catalyzes K27-linked polyubiquitination at lysine 118/442 (HIF-1α) or lysine 117 (HIF-2α). This modification induces proteasomal degradation of HIF-1α, resulting in inhibition of hypoxia signaling. Furthermore, Mylip-deficient bluntsnout bream, zebrafish and mice are more tolerant to hypoxia. These findings reveal a role for MYLIP in regulating hypoxia signaling and identify a target for the development of fish strains with high hypoxia tolerance for the benefit of the aquaculture industry. |
| title | MYLIP attenuates hypoxia tolerance by inducing K27-linked polyubiquitination and subsequent proteasomal degradation of HIF-α. |
| topic | Animals Hypoxia-Inducible Factor 1, alpha Subunit Ubiquitination Proteasome Endopeptidase Complex Zebrafish Ubiquitin-Protein Ligases Mice Hypoxia Humans Basic Helix-Loop-Helix Proteins Proteolysis HEK293 Cells Signal Transduction Lysine Endothelial PAS Domain-Containing Protein 1 |
| url | https://pubmed.ncbi.nlm.nih.gov/40399570/ |