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dc.contributor.authorScholz, Carsten Cen
dc.contributor.authorRodriguez, Javieren
dc.contributor.authorPickel, Christinaen
dc.contributor.authorBurr, Stephenen
dc.contributor.authorFabrizio, Jacqueline-albaen
dc.contributor.authorNolan, Karen Aen
dc.contributor.authorSpielmann, Patricken
dc.contributor.authorCavadas, Miguel ASen
dc.contributor.authorCrifo, Biancaen
dc.contributor.authorHalligan, Doug Nen
dc.contributor.authorNathan, Jamesen
dc.contributor.authorvon, Kriegsheim Alexen
dc.contributor.authorWenger, Roland Hen
dc.contributor.authorPeet, Daniel Jen
dc.contributor.authorCummins, Eoin Pen
dc.contributor.authorTaylor, Cormac Ten
dc.date.accessioned2015-11-10T18:36:01Z
dc.date.available2015-11-10T18:36:01Z
dc.date.issued2016-01-11en
dc.identifier.citationPLoS Biology 2016, 14(1): e1002347. doi:10.1371/journal.pbio.1002347en
dc.identifier.issn1544-9173
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/252577
dc.description.abstractThe 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 endogenous 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, mutant OTUB1 (lacking the hydroxylation site) impairs cellular metabolic processes when compared to wild type cells. Based on these data, we hypothesize that OTUB1 is a target for functional hydroxylation by FIH. We further propose that this provides new insight into the regulation of cellular energy metabolism during hypoxic stress and the potential for targeting hydroxylases for therapeutic benefit.
dc.languageEnglishen
dc.language.isoenen
dc.publisherPLoS
dc.rightsCreative Commons Attribution 4.0 International License
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHydroxylaseen
dc.subjecthypoxiaen
dc.subjectmetabolismen
dc.subjectubiquitinen
dc.subjectdeubiquitinating enzymeen
dc.subjectotubainen
dc.subjectOTU domainen
dc.titleFIH regulates cellular metabolism through hydroxylation of the deubiquitinase OTUB1.en
dc.title.alternativeFIH regulates metabolism through OTUB1en
dc.typeArticle
dc.description.versionThis is the final version of the article. It was first available from PLOS via http://dx.doi.org/10.1371/journal.pbio.1002347en
prism.numbere1002347en
prism.publicationDate2016en
prism.publicationNamePLoS Biologyen
prism.volume14en
dc.rioxxterms.funderWellcome Trust
dcterms.dateAccepted2015-12-07en
rioxxterms.versionofrecord10.1371/journal.pbio.1002347en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2016-01-11en
dc.contributor.orcidBurr, Stephen [0000-0001-8865-126X]
dc.contributor.orcidNathan, James [0000-0002-0248-1632]
dc.identifier.eissn1545-7885
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (102770/Z/13/Z)
pubs.funder-project-idWellcome Trust (100140/Z/12/Z)


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Creative Commons Attribution 4.0 International License
Except where otherwise noted, this item's licence is described as Creative Commons Attribution 4.0 International License