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. Variation...

Full description

Bibliographic Details
Published in:Oncotarget
Main Authors: Bi, Jianling, Hu, Bo, Wang, Jing, Liu, Xing, Zheng, Jinsong, Wang, Ding, Xiao, Wuhan
Format: Text
Language:English
Published: Impact Journals LLC 2017
Subjects:
Research Paper
Beluga
Beluga whale
Beluga*
Online Access:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522066/
http://www.ncbi.nlm.nih.gov/pubmed/28178687
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-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.

Similar Items