FIH Regulates Cellular Metabolism through Hydroxylation of the Deubiquitinase OTUB1
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|Title:||FIH Regulates Cellular Metabolism through Hydroxylation of the Deubiquitinase OTUB1||Authors:||Scholz, Carsten C.
Cavadas, Miguel A. S.
Halligan, Doug N.
Von Kriegsheim, Alex
Cummins, Eoin P.
Taylor, Cormac T.
|Permanent link:||http://hdl.handle.net/10197/9766||Date:||11-Jan-2016||Online since:||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.||Funding Details:||European Commission - Seventh Framework Programme (FP7)
Science Foundation Ireland
|Type of material:||Journal Article||Publisher:||Public Library of Science||Journal:||PLOS Biology||Volume:||14||Issue:||1||Copyright (published version):||2016 the Authors||Keywords:||Hydroxylase; Hypoxia; Metabolism; Ubiquitin; Deubiquitinating enzyme; Otubain; OTU domain||DOI:||10.1371/journal.pbio.1002347||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||Conway Institute Research Collection|
SBI Research Collection
Medicine Research Collection
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