Beluga whale pVHL enhances HIF-2α activity via inducing HIF-2α proteasomal degradation under hypoxia.
Aquatic mammals, such as cetaceans experience various depths, with accordingly diverse oxygenation, thus, cetaceans have developed adaptations for hypoxia, but mechanisms underlying this tolerance to low oxygen are unclear. Here we analyzed VHL and HIF-2α, in the hypoxia signaling pathway. Variations in VHL are greater than HIF-2α between cetaceans and terrestrial mammals, and beluga whale VHL (BW-VHL) promotes HIF-2α degradation under hypoxia. BW-VHL catalyzes BW-HIF-2α to form K48-linked poly-ubiquitin chains mainly at the lysine 429 of BW-HIF-2α (K429) and induces BW-HIF-2α for proteasomal degradation. W100 within BW-VHL is a key site for BW-VHL functionally and BW-VHL enhances transcriptional activity of BW-HIF-2α under hypoxia. Our data therefore reveal that BW-VHL has a unique function that may contribute to hypoxic adaptation.
The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, P. R. China.
Jianling
J
Bi
The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, P. R. China.
Bo
B
Hu
The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, P. R. China.
Jing
J
Wang
The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, P. R. China.
Xing
X
Liu
The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, P. R. China.
Jinsong
J
Zheng
The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, P. R. China.
Ding
D
Wang
The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, P. R. China.|State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, P. R. China.
Wuhan
W
Xiao
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D050643:Beluga Whale; D002384:Catalysis; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D055550:Protein Stability; D059748:Proteolysis; D015533:Transcriptional Activation; D054875:Ubiquitination; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism*; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D046988:Proteasome Endopeptidase Complex; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000099162:Endothelial PAS Domain-Containing Protein 1
HIF-2α; VHL; beluga whale; cetaceans; hypoxia