Beluga whale pVHL enhances HIF-2 alpha activity via inducing HIF-2 alpha 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-2 alpha, in the hypoxia signaling pathway. Vari...

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Bibliographic Details
Published in:Oncotarget
Main Authors: Bi, Jianling, Hu, Bo, Wang, Jing, Liu, Xing, Zheng, Jinsong, Wang, Ding, Xiao, Wuhan
Format: Report
Language:English
Published: IMPACT JOURNALS LLC 2017
Subjects:
beluga whale
cetaceans
hypoxia
HIF-2 alpha
VHL
Oncology
Cell Biology
TUMOR-SUPPRESSOR PROTEIN
HIGH-ALTITUDE ADAPTATION
BAIJI LIPOTES-VEXILLIFER
DELPHINAPTERUS-LEUCAS
HIF-ALPHA
MOLE-RAT
FINLESS PORPOISE
DIVING BEHAVIOR
YANGTZE-RIVER
WHITE WHALES
Beluga
Beluga whale
Beluga*
Delphinapterus leucas
Online Access:http://ir.ihb.ac.cn/handle/342005/31444
http://ir.ihb.ac.cn/handle/342005/31445
https://doi.org/10.18632/oncotarget.15038
Description
Summary: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-2 alpha, in the hypoxia signaling pathway. Variations in VHL are greater than HIF-2 alpha between cetaceans and terrestrial mammals, and beluga whale VHL (BW-VHL) promotes HIF-2 alpha degradation under hypoxia. BW-VHL catalyzes BW-HIF-2 alpha to form K48-linked polyubiquitin chains mainly at the lysine 429 of BW-HIF-2 alpha (K429) and induces BW-HIF-2 alpha for proteasomal degradation. W100 within BW-VHL is a key site for BW-VHL functionally and BW-VHL enhances transcriptional activity of BW-HIF-2 alpha under hypoxia. Our data therefore reveal that BW-VHL has a unique function that may contribute to hypoxic adaptation.

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