Beluga whale pVHL enhances HIF-2&#x03B1; activity via inducing HIF-2&#x03B1; proteasomal degradation under hypoxia

Jianling Bi; Bo Hu; Jing Wang; Xing Liu; Jinsong Zheng; Ding Wang; Wuhan Xiao

doi:10.18632/oncotarget.15038

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Research Papers:

Beluga whale pVHL enhances HIF-2α activity via inducing HIF-2α proteasomal degradation under hypoxia

Jianling Bi, Bo Hu, Jing Wang, Xing Liu, Jinsong Zheng, Ding Wang and Wuhan Xiao _

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Oncotarget. 2017; 8:42272-42287. https://doi.org/10.18632/oncotarget.15038

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Abstract

Jianling Bi1, Bo Hu1, Jing Wang1, Xing Liu1, Jinsong Zheng1, Ding Wang1 and Wuhan Xiao1,2

1The Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, P. R. China

2State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, P. R. China

Correspondence to:

Wuhan Xiao, email: [email protected]

Ding Wang, email: [email protected]

Keywords: beluga whale, cetaceans, hypoxia, HIF-2α, VHL

Received: October 09, 2016 Accepted: January 09, 2017 Published: February 02, 2017

ABSTRACT

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.

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PII: 15038

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Research Papers:

Beluga whale pVHL enhances HIF-2α activity via inducing HIF-2α proteasomal degradation under hypoxia

Abstract