Sirtuins: Sir2-related NAD-dependent protein deacetylases

By Brian J. North, E. Verdin. Genome Biology, 2004

603 citations recorded by the source corpus.

SummarySilent information regulator 2 (Sir2) proteins, or sirtuins, are protein deacetylases dependent on nicotine adenine dinucleotide (NAD) and are found in organisms ranging from bacteria to humans. In eukaryotes, sirtuins regulate transcriptional repression, recombination, the cell-division cycle, microtubule organization, and cellular responses to DNA-damaging agents. Sirtuins have also been implicated in regulating the molecular mechanisms of aging. The Sir2 catalytic domain, which is shared among all sirtuins, consists of two distinct domains that bind NAD and the acetyl-lysine substrate, respectively. In addition to the catalytic domain, eukaryotic sirtuins contain variable amino- and carboxy-terminal extensions that regulate their subcellular localizations and catalytic activity.

Subfields: Epidemiology, Geriatrics and Gerontology, Physiology

View Paper: https://www.semanticscholar.org/paper/3c8a4e988e1b0be554c702a3e807bcf5e6b724f8

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. E. Verdin
2. F. Alt

In Geriatrics and Gerontology

1. E. Verdin
2. L. Saunders
3. T. Arnesen
4. Rasmus Ree
5. Adrian Drazic
6. Line M. Myklebust
7. W. Gu
8. Ray-Whay Chiu Yen

In Physiology

1. E. Verdin
2. W. Gu
3. L. Saunders
4. F. Alt
5. R. Mostoslavsky
6. E. Michishita

Citations in the corpus

• Sirtuins: critical regulators at the crossroads between cancer and aging (2007, background): “The deacetylase domain in the sirtuins is different from that of class I and II HDACs, which are Znþ - dependent enzymes (North and Verdin, 2004; Longo and Kennedy, 2006).”
• SIRT1 controls endothelial angiogenic functions during vascular growth. (2007, background): “HDACs are divided into three classes based on their homology with yeast proteins Rpd3 (class I), Hda1 (class II), and Sir2 (class III) (de Ruijter et al. 2003; North and Verdin 2004).”
• HAMAP in 2015: updates to the protein family classification and annotation system (2014, background): “Specificity for these relatively bulky substrates may be conferred by a larger hydrophobic pocket and substrate-binding residues (Tyr-102 and Arg-105 in human SIR5) common to all class III sirtuins from all kingdoms of life (20,30).”
• Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. (2005, background): “…metabolism (Merry, 2004) and that the sirtuin family of proteins function in a NAD+-dependent manner (Imai et al., 2000; Blander and Guarente, 2004; North and Verdin, 2004), an interesting possibility is that one or more of the 18 mitochondrial SIRT proteins may function in linking metabolic and…”
• Expert curation in UniProtKB: a case study on dealing with conflicting and erroneous data (2014, neutral): “Mammals have seven sirtuins, SIRT1–SIRT7 (9).”
• Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses. (2005, background): “In mammals there are seven homologs of yeast Sir2p, termed sirtuins, with nuclear protein SIRT1 having the highest homology (reviewed by North and Verdin, 2004).”
• The world of protein acetylation. (2016, background): “Noteworthy, class I and II share a high homology in their catalytic domains [209].”
• Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. (2006, neutral): “North and Verdin, 2004).”