PUBLICATION
TRIM25 enhances hypoxia signaling by catalyzing K11-linked polyubiquitination and stabilization of HIF-α
- Authors
- Li, Z., Li, J., Li, Z., Wang, R., Yuan, L., Song, Y., Wang, Y., Yan, R., Lai, F., Wang, J., Xiao, W.
- ID
- ZDB-PUB-260509-8
- Date
- 2026
- Source
- The Journal of biological chemistry : 113125113125 (Journal)
- Registered Authors
- Li, Zhi, Wang, Jing, Xiao, Wuhan
- Keywords
- HIF-α, Hypoxia signaling, TRIM25, Ubiquitination
- MeSH Terms
- none
- PubMed
- 42103230 Full text @ J. Biol. Chem.
Citation
Li, Z., Li, J., Li, Z., Wang, R., Yuan, L., Song, Y., Wang, Y., Yan, R., Lai, F., Wang, J., Xiao, W. (2026) TRIM25 enhances hypoxia signaling by catalyzing K11-linked polyubiquitination and stabilization of HIF-α. The Journal of biological chemistry. :113125113125.
Abstract
TRIM25 is an E3 ubiquitin ligase involved in various cellular processes due to its enzymatic activity. In particular, it plays a role in antiviral innate immunity. Here, we demonstrate that TRIM25 modulates hypoxia signaling. TRIM25 interacts with HIF-1α and HIF-2α, stabilizing them. TRIM25 catalyzes K11-linked polyubiquitination of HIF-1α at K719 and K721 and of HIF-2α at K709. This results in the stabilization of the proteins and enhanced hypoxia signaling. Moreover, TRIM25-mediated augmentation of hypoxia signaling depends on HIF-1α. Trim25-deficient mice are more sensitive to hypoxia, and zebrafish lacking trim25 show a similar phenotype. These data reveal TRIM25's role in regulating hypoxia signaling and provide insight into a new mechanism that modulates the stabilization and activity of HIF-1α and HIF-2α.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping