ArticleProceedings of the National Academy of Sciences of the United States of America2019
Identification of evolutionary and kinetic drivers of NAD-dependent signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 67 citations in OpenAlex.
- Lactylation at lysine 145 fosters KAT8-TIP60 complex formation to promote p53 acetylation at lysine 120 and its pro-apoptotic function.Nature communications · 2026Article
- Nicotinamide salvage is required for proliferation and sustaining self-renewal in undifferentiated embryonic stem cells.Stem cells (Dayton, Ohio) · 2026Article
- Timing of NAD Deficiency During Organogenesis Dictates Defect Type and Penetrance.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Nicotinamide N-Methyl Transferase (NNMT) Sustains Innate Sensitivity to NAMPT Inhibition in YAP-dependent Stem-like/Mesenchymal Prostate Cancer.International journal of biological sciences · 2026Article
- NAMPT and NNMT released via extracellular vesicles and as soluble mediators are distinguished traits of BRAF inhibitor resistance of melanoma cells impacting on the tumor microenvironment.Cell communication and signaling : CCS · 2025Article
- ProTaxoVis-protein taxonomic visualisation of presence.BMC bioinformatics · 2025Article
- Nicotinamide N-Methyltransferase (NNMT) and Liver Cancer: From Metabolic Networks to Therapeutic Targets.Biomolecules · 2025Review
- Pathobiochemistry of Aging and Neurodegeneration: Deregulation of NAD+ Metabolism in Brain Cells.Biomolecules · 2024Review
- Regulation of and challenges in targeting NADNature reviews. Molecular cell biology · 2024Review
- Nicotinamide N-Methyltransferase (NNMT): A New Hope for Treating Aging and Age-Related Conditions.Metabolites · 2024Review
- Structural insights into Xanthomonas campestris pv. campestris NADCommunications biology · 2024Article
- Control of NADThe EMBO journal · 2024Article
- Phosphoribosyltransferases and Their Roles in Plant Development and Abiotic Stress Response.International journal of molecular sciences · 2023Review
- NAD precursors cycle between host tissues and the gut microbiome.Cell metabolism · 2022Article
- Sirtuin Evolution at the Dawn of Animal Life.Molecular biology and evolution · 2022Article
- Current Uncertainties and Future Challenges Regarding NAD+ Boosting Strategies.Antioxidants (Basel, Switzerland) · 2022Review
- NADMetabolites · 2022Review
- Glioblastoma and Methionine Addiction.International journal of molecular sciences · 2022Review
- Early Evolutionary Selection of NAD Biosynthesis Pathway in Bacteria.Metabolites · 2022Article
- COVID-19: Are We Facing Secondary Pellagra Which Cannot Simply Be Cured by Vitamin B3?International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nicotinamide adenine dinucleotide (NAD) provides an important link between metabolism and signal transduction and has emerged as central hub between bioenergetics and all major cellular events. NAD-dependent signaling (e.g., by sirtuins and poly-adenosine diphosphate [ADP] ribose polymerases [PARPs]) consumes considerable amounts of NAD. To maintain physiological functions, NAD consumption and biosynthesis need to be carefully balanced. Using extensive phylogenetic analyses, mathematical modeling of NAD metabolism, and experimental verification, we show that the diversification of NAD-dependent signaling in vertebrates depended on 3 critical evolutionary events: 1) the transition of NAD biosynthesis to exclusive usage of nicotinamide phosphoribosyltransferase (NamPT); 2) the occurrence of nicotinamide N-methyltransferase (NNMT), which diverts nicotinamide (Nam) from recycling into NAD, preventing Nam accumulation and inhibition of NAD-dependent signaling reactions; and 3) structural adaptation of NamPT, providing an unusually high affinity toward Nam, necessary to maintain NAD levels. Our results reveal an unexpected coevolution and kinetic interplay between NNMT and NamPT that enables extensive NAD signaling. This has implications for therapeutic strategies of NAD supplementation and the use of NNMT or NamPT inhibitors in disease treatment.
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