Research
| Title： | MYLIP attenuates hypoxia tolerance by inducing K27-linked polyubiquitination and subsequent proteasomal degradation of HIF-α |
|---|---|
| First author： | Li, Jun; Li, Zhi; Li, Xiong; Li, Ziyi; Song, Yanan; Yuan, Le; Wang, Yanyi; Yan, Runkun; Lai, Fuxiang; Wang, Jing; Xiao, Wuhan |
| Journal： | COMMUNICATIONS BIOLOGY |
| Years： | 2025 |
| DOI： | 10.1038/s42003-025-08200-x |
| Abstract： | Hypoxia tolerance is mainly controlled by the hypoxia signaling pathway and HIF-1 alpha/2 alpha 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-2 alpha and a negative regulator of both HIF-1 alpha and HIF-2 alpha. MYLIP interacts with HIF-1 alpha/2 alpha and catalyzes K27-linked polyubiquitination at lysine 118/442 (HIF-1 alpha) or lysine 117 (HIF-2 alpha). This modification induces proteasomal degradation of HIF-1 alpha, 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. |
