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| Main Authors: | , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Communications biology
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40399570/ |
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Table of 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.