Sara Duarte-Pereira, Sérgio Matos, José Luís Oliveira, Raquel M Silva
{"title":"对NAD相互作用蛋白的研究强调了NAD在细胞中的调节作用及其作为治疗靶点的潜力。","authors":"Sara Duarte-Pereira, Sérgio Matos, José Luís Oliveira, Raquel M Silva","doi":"10.1515/jib-2022-0049","DOIUrl":null,"url":null,"abstract":"<p><p>Nicotinamide 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 <i>NAD-binding proteins</i> (<i>NADBPs</i>) dataset - and of proteins that interact with NADBPs - the <i>NAD-protein-protein interactions</i> (<i>NAD-PPIs</i>) 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.</p>","PeriodicalId":53625,"journal":{"name":"Journal of Integrative Bioinformatics","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10389049/pdf/","citationCount":"0","resultStr":"{\"title\":\"Study of NAD-interacting proteins highlights the extent of NAD regulatory roles in the cell and its potential as a therapeutic target.\",\"authors\":\"Sara Duarte-Pereira, Sérgio Matos, José Luís Oliveira, Raquel M Silva\",\"doi\":\"10.1515/jib-2022-0049\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Nicotinamide 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 <i>NAD-binding proteins</i> (<i>NADBPs</i>) dataset - and of proteins that interact with NADBPs - the <i>NAD-protein-protein interactions</i> (<i>NAD-PPIs</i>) 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.</p>\",\"PeriodicalId\":53625,\"journal\":{\"name\":\"Journal of Integrative Bioinformatics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2023-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10389049/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Integrative Bioinformatics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1515/jib-2022-0049\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MATHEMATICAL & COMPUTATIONAL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Integrative Bioinformatics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1515/jib-2022-0049","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MATHEMATICAL & COMPUTATIONAL BIOLOGY","Score":null,"Total":0}
Study of NAD-interacting proteins highlights the extent of NAD regulatory roles in the cell and its potential as a therapeutic target.
Nicotinamide 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.