Source: N-terminal His-tagged SIRT6 (amino acids 1-355) purified from E. coli · M_r: 43.7 kDa · The sirtuins represent a distinct class of trichostatin A-insensitive lysyl-deacetylases (class III HDACs) and have been shown to catalyze a reaction that couples lysine deacetylation to the formation of nicotinamide and O-acetyl-ADP-ribose from NAD⁺ and the abstracted acetyl group.^1,2,3 There are seven human sirtuins, which have been designated SIRT1-7.⁴ SIRT6 associates specifically with telomeres and functions at chromatin to decrease NF-κB signaling.^5,6 Mammalian cells depleted of SIRT6 display abnormal telomere structures similar to defects found in Werner syndrome, a premature ageing disorder, and have a shortened life span.^6,5 Since SIRT6 binds and attenuates NF-κB signaling, it is proposed that activators of SIRT6 may be effective anti-cancer and anti-inflammatory drugs and may increase longevity.⁵

1 Imai, S., Armstrong, C.M., Kaeberlein, M., et al. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403 795-800 (2000).

2 Tanner, K.G., Landry, J., Sternglanz, R., et al. Silent information regulator 2 family of NAD-dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose. Proc Natl Acad Sci USA 97(26) 14178-14182 (2000).

3 Tanny, J.C., and Moazed, D. Coupling of histone deacetylation to NAD breakdown by the yeast silencing protein Sir2: Evidence for acetyl transfer from substrate to an NAD breakdown product. Proc Natl Acad Sci USA 98(2) 415-420 (2001).

4 Frye, R.A. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun 273 793-798 (2000).

5 Kawahara, T.L.A., Michishita, E., Adler, A.S., et al. SIRT6 links histone H3 lysine 9 deacetylation to NF-kB-dependent gene expression and organismal life span. Cell 136 62-74 (2009).

6 Michishita, E., McCord, R.A., Berber, E., et al. SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature 452 492-496 (2008).

Kawahara, T.L.A., Michishita, E., Adler, A.S., et al. SIRT6 links histone H3 lysine 9 deacetylation to NF-kB-dependent gene expression and organismal life span. Cell 136 62-74 (2009).

Frye, R.A. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun 273 793-798 (2000).

Tanner, K.G., Landry, J., Sternglanz, R., et al. Silent information regulator 2 family of NAD-dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose. Proc Natl Acad Sci USA 97(26) 14178-14182 (2000).

Michishita, E., McCord, R.A., Berber, E., et al. SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature 452 492-496 (2008).

Tanny, J.C., and Moazed, D. Coupling of histone deacetylation to NAD breakdown by the yeast silencing protein Sir2: Evidence for acetyl transfer from substrate to an NAD breakdown product. Proc Natl Acad Sci USA 98(2) 415-420 (2001).

Imai, S., Armstrong, C.M., Kaeberlein, M., et al. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403 795-800 (2000).

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