ArticleProceedings of the National Academy of Sciences of the United States of America2000
The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 458 papers.
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Who cites it
458 citing papers in PubMed, 962 citations in OpenAlex.
- Defective expression of SIRT1 contributes to sustain inflammatory pathways in the gut.Mucosal immunology · 2014Trial
- Epigenetic Control of Mammalian Cardiomyocyte Proliferation.Current cardiology reports · 2026Review
- Cohesin sumoylation is required for repression of subtelomeric gene expression in Saccharomyces cerevisiae.Journal of cell science · 2026Article
- The Pof1 nicotinamide mononucleotide adenylyl transferase has a non-canonical role in NADThe Journal of biological chemistry · 2026Article
- The deacetylase Sir2 is the primary sensor driving transcriptional changes in response to low NAD+ in the yeast Kluyveromyces lactis.Genetics · 2026Article
- Unveiling the Potential of Functional Components in Hull-Less Barley Grains: Health Benefits, Structural Composition, and Genetic Advancements.Foods (Basel, Switzerland) · 2026Review
- Differential regulation of SIRT5 activity by reduced nicotinic acid riboside (NARH).RSC chemical biology · 2026Article
- Carba-NAD binding activates SIR2 by reshaping conformational plasticity and rewiring long-range allosteric networks.PLoS computational biology · 2026Article
- The nicotinamide mononucleotide adenylyl transferase (NMNAT/Nma1) modulates phosphate-sensing (PHO) signaling independent of its NAD+ synthesis activity in Saccharomyces cerevisiae.FEMS yeast research · 2026Article
- Metabolic and post-translational modifications in sepsis-associated immune dysfunction: a conceptual framework.Frontiers in immunology · 2026Review
- Mitochondrial remodeling in heart failure with reduced ejection fraction.Frontiers in physiology · 2026Review
- Simulated Microgravity-Induced Changes in SUMOylation and Protein Expression inInternational journal of molecular sciences · 2025Article
- Global Transcriptomic Analysis Identifies Gene Expression Programs Regulated by α-Factor in Yeast.Journal of microbiology and biotechnology · 2025Article
- Filament formation and NAD processing by noncanonical human FAM118 sirtuins.Nature structural & molecular biology · 2025Article
- NADCells · 2025Review
- The Roles of Moonlighting Nicotinamide Mononucleotide Adenylyl Transferases in Cell Physiology.International journal of molecular sciences · 2025Review
- CRISPR-Cas9 targeting of G-Quadruplex DNA in ADH1 promoter highlights its role in transcriptome and metabolome regulation.Nucleic acids research · 2025Article
- Sirtuin 1 Activation Mitigates Murine Vasculitis Severity by Promoting Autophagy and Mitophagy.bioRxiv : the preprint server for biology · 2025Article
- The impact of mitochondrial dysfunction on osteoarthritis cartilage: current insights and emerging mitochondria-targeted therapies.Bone research · 2025Review
- NADCommunications biology · 2025Article
398 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Homologs of the chromatin-bound yeast silent information regulator 2 (SIR2) protein are found in organisms from all biological kingdoms. SIR2 itself was originally discovered to influence mating-type control in haploid cells by locus-specific transcriptional silencing. Since then, SIR2 and its homologs have been suggested to play additional roles in suppression of recombination, chromosomal stability, metabolic regulation, meiosis, and aging. Considering the far-ranging nature of these functions, a major experimental goal has been to understand the molecular mechanism(s) by which this family of proteins acts. We report here that members of the SIR2 family catalyze an NAD-nicotinamide exchange reaction that requires the presence of acetylated lysines such as those found in the N termini of histones. Significantly, these enzymes also catalyze histone deacetylation in a reaction that absolutely requires NAD, thereby distinguishing them from previously characterized deacetylases. The enzymes are active on histone substrates that have been acetylated by both chromatin assembly-linked and transcription-related acetyltransferases. Contrary to a recent report, we find no evidence that these proteins ADP-ribosylate histones. Discovery of an intrinsic deacetylation activity for the conserved SIR2 family provides a mechanism for modifying histones and other proteins to regulate transcription and diverse biological processes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.