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Study of NAD-interacting proteins highlights the extent of NAD regulatory roles in the cell and its potential as a therapeutic target

2023-06-01Journal article Open access
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dc.contributor.authorDuarte-Pereira, Sara
dc.contributor.authorMatos, Sérgio
dc.contributor.authorOliveira, José Luís
dc.contributor.authorSilva, Raquel M.
dc.date.accessioned2023-03-22T09:42:20Z
dc.date.available2023-03-22T09:42:20Z
dc.date.issued2023-06-01
dc.description.abstractNicotinamide adenine dinucleotide (NAD) levels are essential for the normal physiology of the cell and are strictly regulated to prevent pathological conditions. NAD functions as a coenzyme in redox reactions, as a substrate of regulatory proteins, and as a mediator of protein-protein interactions. The main objectives of this study were to identify the NAD-binding and NAD-interacting proteins, and to uncover novel proteins and functions that could be regulated by this metabolite. It was considered if cancer-associated proteins were potential therapeutic targets. Using multiple experimental databases, we defined datasets of proteins that directly interact with NAD – the NAD-binding proteins (NADBPs) dataset – and of proteins that interact with NADBPs – the NAD-protein–protein interactions (NAD-PPIs) dataset. Pathway enrichment analysis revealed that NADBPs participate in several metabolic pathways, while NAD-PPIs are mostly involved in signalling pathways. These include disease-related pathways, namely, three major neurodegenerative disorders: Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease. Then, the complete human proteome was further analysed to select potential NADBPs. TRPC3 and isoforms of diacylglycerol (DAG) kinases, which are involved in calcium signalling, were identified as new NADBPs. Potential therapeutic targets that interact with NAD were identified, that have regulatory and signalling functions in cancer and neurodegenerative diseases.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1515/jib-2022-0049pt_PT
dc.identifier.eid85166395317
dc.identifier.issn1613-4516
dc.identifier.pmid36880517
dc.identifier.urihttp://hdl.handle.net/10400.14/40664
dc.identifier.wos000945945600001
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectCancerpt_PT
dc.subjectInteractomept_PT
dc.subjectNAD metabolismpt_PT
dc.subjectNeurodegenerative disorderspt_PT
dc.subjectSignallingpt_PT
dc.titleStudy of NAD-interacting proteins highlights the extent of NAD regulatory roles in the cell and its potential as a therapeutic targetpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue2
oaire.citation.titleJournal of integrative bioinformaticspt_PT
oaire.citation.volume20
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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