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dc.contributor.authorBockwoldt, Mathias
dc.contributor.authorHoury, Dorothee
dc.contributor.authorNiere, Marc
dc.contributor.authorGossmann, Toni I.
dc.contributor.authorReinartz, Ines
dc.contributor.authorSchug, Alexander
dc.contributor.authorZiegler, Mathias
dc.contributor.authorHeiland, Ines
dc.date.accessioned2019-12-03T14:05:04Z
dc.date.available2019-12-03T14:05:04Z
dc.date.issued2019-07-24
dc.description.abstractNicotinamide adenine dinucleotide (NAD) is best known as an essential cofactor of biochemical reactions. In addition, it is involved in the regulation of virtually all major cellular events. These NAD-dependent regulatory functions are mediated by enzymes (e.g., sirtuins, poly–adenosine -diphosphate [ADP] ribose polymerases, ADP-ribosyl cyclases) that cleave the molecule to liberate nicotinamide (Nam). We show that diversification of NAD-dependent signaling in Deuterostomia was accompanied by an optimization of NAD biosynthesis to ensure efficient high-affinity recycling of Nam into NAD through Nam phosphoribosyltransferase (NamPT). In addition, a Nam N-methyltransferase (NNMT) emerged, which facilitates high NAD-dependent signaling turnover by preventing accumulation of inhibitory Nam. This unexpected kinetic interplay between NamPT and NNMT needs to be considered in therapeutic strategies targeting these enzymes.en_US
dc.descriptionCopyright 2019 National Academy of Sciencesen_US
dc.identifier.citationBockwoldt, M., Houry, D., Niere, M., Gossmann, T.I., Reinartz, I., Schug, A., Ziegler, M. & Heiland, I. (2019). Identification of evolutionary and kinetic drivers of NAD-dependent signaling. <i>Proceedings of the National Academy of Sciences of the United States of America, 116</i>(32), 15957-15966. https://doi.org/10.1073/pnas.1902346116en_US
dc.identifier.cristinIDFRIDAID 1719004
dc.identifier.doihttps://doi.org/10.1073/pnas.1902346116
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.urihttps://hdl.handle.net/10037/16777
dc.language.isoengen_US
dc.publisherNational Academy of Sciences of the USAen_US
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/754688/EU/Systems Medicine of Metabolic-Signaling Networks: A New Concept for Breast Cancer Patient Stratification/MESI-STRAT/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/FRIMED2/250395/Norway/The NAD metabolome of human cells - understanding a fundamental metabolic and signalling network//en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Mathematics and natural science: 400::Basic biosciences: 470::Molecular biology: 473en_US
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Molekylærbiologi: 473en_US
dc.titleIdentification of evolutionary and kinetic drivers of NAD-dependent signalingen_US
dc.type.versionacceptedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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