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  5. FIH Regulates Cellular Metabolism through Hydroxylation of the Deubiquitinase OTUB1
 
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FIH Regulates Cellular Metabolism through Hydroxylation of the Deubiquitinase OTUB1

Author(s)
Scholz, Carsten C.  
Rodriguez, Javier  
Pickel, Christina  
Cavadas, Miguel A. S.  
Crifo, Bianca  
Halligan, Doug N.  
Kriegsheim, Alexander von  
Cummins, Eoin P.  
Taylor, Cormac T.  
et al.  
Uri
http://hdl.handle.net/10197/9766
Date Issued
2016-01-11
Date Available
2019-04-02T08:40:22Z
Abstract
The asparagine hydroxylase, factor inhibiting HIF (FIH), confers oxygen-dependence upon the hypoxia-inducible factor (HIF), a master regulator of the cellular adaptive response to hypoxia. Studies investigating whether asparagine hydroxylation is a general regulatory oxygen-dependent modification have identified multiple non-HIF targets for FIH. However, the functional consequences of this outside of the HIF pathway remain unclear. Here, we demonstrate that the deubiquitinase ovarian tumor domain containing ubiquitin aldehyde binding protein 1 (OTUB1) is a substrate for hydroxylation by FIH on N22. Mutation of N22 leads to a profound change in the interaction of OTUB1 with proteins important in cellular metabolism. Furthermore, in cultured cells, overexpression of N22A mutant OTUB1 impairs cellular metabolic processes when compared to wild type. Based on these data, we hypothesize that OTUB1 is a target for functional hydroxylation by FIH. Additionally, we propose that our results provide new insight into the regulation of cellular energy metabolism during hypoxic stress and the potential for targeting hydroxylases for therapeutic benefit.
Sponsorship
European Commission - Seventh Framework Programme (FP7)
Science Foundation Ireland
Wellcome Trust
Other Sponsorship
Australian Research Council
University of Zurich
Swiss National Science Foundation
Systems Biology Ireland
Type of Material
Journal Article
Publisher
Public Library of Science
Journal
PLOS Biology
Volume
14
Issue
1
Copyright (Published Version)
2016 the Authors
Subjects

Hydroxylase

Hypoxia

Metabolism

Ubiquitin

Deubiquitinating enzy...

Otubain

OTU domain

DOI
10.1371/journal.pbio.1002347
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
https://creativecommons.org/licenses/by-nc-nd/3.0/ie/
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FIH regulates cellular metabolism through hydroxylation of the deubiquitinase OTUB1. CTaylor.pdf

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467.69 KB

Format

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Checksum (MD5)

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Owning collection
SBI Research Collection
Mapped collections
Conway Institute Research Collection•
Medicine Research Collection

Item descriptive metadata is released under a CC-0 (public domain) license: https://creativecommons.org/public-domain/cc0/.
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