PUBLICATION
MYLIP attenuates hypoxia tolerance by inducing K27-linked polyubiquitination and subsequent proteasomal degradation of HIF-α
- Authors
- Li, J., Li, Z., Li, X., Li, Z., Song, Y., Yuan, L., Wang, Y., Yan, R., Lai, F., Wang, J., Xiao, W.
- ID
- ZDB-PUB-250522-10
- Date
- 2025
- Source
- Communications biology 8: 774774 (Journal)
- Registered Authors
- Li, Xiong, Wang, Jing, Xiao, Wuhan
- Keywords
- none
- MeSH Terms
-
- Proteolysis
- Proteasome Endopeptidase Complex*/metabolism
- Mice
- Humans
- Zebrafish
- Basic Helix-Loop-Helix Proteins*/genetics
- Basic Helix-Loop-Helix Proteins*/metabolism
- Ubiquitination*
- Hypoxia*/metabolism
- Signal Transduction
- Hypoxia-Inducible Factor 1, alpha Subunit*/genetics
- Hypoxia-Inducible Factor 1, alpha Subunit*/metabolism
- HEK293 Cells
- Animals
- Lysine/metabolism
- Ubiquitin-Protein Ligases*/genetics
- Ubiquitin-Protein Ligases*/metabolism
- PubMed
- 40399570 Full text @ Commun Biol
Citation
Li, J., Li, Z., Li, X., Li, Z., Song, Y., Yuan, L., Wang, Y., Yan, R., Lai, F., Wang, J., Xiao, W. (2025) MYLIP attenuates hypoxia tolerance by inducing K27-linked polyubiquitination and subsequent proteasomal degradation of HIF-α. Communications biology. 8:774774.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping