Zebrafish usp3 loss promotes hypoxic tolerance by disrupting deubiquitination of K63-polyubiquitinated hif-1αa  

作　　者：Jun Li Ziwen Zhou Xiaolian Cai Yanan Song Zhi Li Ziyi Li Wuhan Xiao Jing Wang 

机构地区：[1]State Key Laboratory of Freshwater Ecology and Biotechnology,Institute of Hydrobiology,Chinese Academy of Sciences,Wuhan,430072,PR China [2]Hubei Hongshan Laboratory,Wuhan,430070,PR China [3]University of Chinese Academy of Sciences,Beijing,100049,PR China [4]The Innovation of Seed Design,Chinese Academy of Sciences,Wuhan,430072,PR China

出　　处：《Water Biology and Security》2024年第2期17-30,共14页水生生物与安全（英文）

基　　金：NSFC[31721005 and 31830101 to W.X,31972786 to J.W.];The Strategic Priority Research Program of the Chinese Academy of Sciences[XDA24010308 to W.X.].

摘　　要：The hypoxia-inducible factor(HIF)-mediated hypoxia signaling pathway influences oxygen homeostasis in aerobic organisms.This pathway is regulated by several other pathways.Elucidation of its regulation and the underlying mechanisms may provide insights into the strategies of adaptation and tolerance of organisms to hypoxia.In this study,we found that loss of ubiquitin-specific protease 3(usp3)in zebrafish promotes hypoxia tolerance.Zebrafish usp3 specifically binds to hif-1αa and induces its proteasomal degradation,which is dependent on its deubiquitinase activity.This process leads to the suppression of hypoxia signaling under hypoxia.In addition,usp3 catalyzes the deubiquitination of K63-polyubiquitinated hif-1αa.Endogenous evidence indicated that mammalian USP3 behaves like zebrafish usp3 in regulating the activity of HIF-1α.These findings revealed a novel role for usp3 in influencing hypoxia signaling and showed that usp3-mediated HIF-1αdegradation impairs hypoxia signaling,leading to a decrease in hypoxia tolerance.

关 键 词：Hif-1αa HIF-1Α Hypoxic tolerance usp3 ZEBRAFISH 

分 类 号：Q95[生物学—动物学]