Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/98085
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Type: Journal article
Title: FIH regulates cellular metabolism through hydroxylation of the deubiquitinase OTUB1
Author: Scholz, C.
Rodriguez, J.
Pickel, C.
Burr, S.
Fabrizio, J.
Nolan, K.
Spielmann, P.
Cavadas, M.
Crifo, B.
Halligan, D.
Nathan, J.
Peet, D.
Wenger, R.
Von Kriegsheim, A.
Cummins, E.
Taylor, C.
Citation: PLoS Biology, 2016; 14(1):e1002347-1-e1002347-22
Publisher: Public Library of Science
Issue Date: 2016
ISSN: 1544-9173
1545-7885
Statement of
Responsibility: 
Carsten C. Scholz, Javier Rodriguez, Christina Pickel, Stephen Burr, Jacqueline-alba Fabrizio, Karen A. Nolan, Patrick Spielmann, Miguel A. S. Cavadas, Bianca Crifo, Doug N. Halligan, James A. Nathan, Daniel J. Peet, Roland H. Wenger, Alex Von Kriegsheim, Eoin P. Cummins, Cormac T. Taylor
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.
Keywords: Humans; Cysteine Endopeptidases; Mixed Function Oxygenases; Repressor Proteins; Mutagenesis, Site-Directed; Energy Metabolism; Hydroxylation; AMP-Activated Protein Kinases; Protein Stability; HEK293 Cells
Description: Published: January 11, 2016
Rights: © 2016 Scholz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
RMID: 0030041510
DOI: 10.1371/journal.pbio.1002347
Grant ID: http://purl.org/au-research/grants/arc/DP150102860
Appears in Collections:Molecular and Biomedical Science publications

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