Source: recombinant N-terminal GST-tagged SIRT1 amino acids 193-747 purified from E. coli · M_r: 89.2 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 SIRT1, which is located in the nucleus, is the human sirtuin with the greatest homology to yeast Sir2 (Silent information regulator 2) and has been shown to regulate the activity of the p53 tumor suppressor and inhibit apoptosis.^5,6,7 These results have significant implications regarding an important role of SIRT1 in modulating the sensitivity of cells in the p53-dependent apoptotic response and the possible effect in cancer therapy. Since the growth suppressive function of p53 is strongly enhanced by DNA damaging reagents, it is expected that inhibitors of SIRT1 may be effective anti-cancer drugs.⁸

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 Luo, J., Nikolaev, A.Y., Imai, S., et al. Negative control of p53 by Sir2α promotes cell survival under stress. Cell 107 137-148 (2001).

6 Vaziri, H., Dessain, S.K., Eaton, E.N., et al. hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase. Cell 107 149-159 (2001).

7 Langley, E., Pearson, M., Faretta, M., et al. Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J 21(10) 2383-2396 (2002).

8 Longo, V.D., and Kennedy, B.K. Sirtuins in aging and age-related disease. Cell 126 257-268 (2006).

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).

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).

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).

Longo, V.D., and Kennedy, B.K. Sirtuins in aging and age-related disease. Cell 126 257-268 (2006).

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

Luo, J., Nikolaev, A.Y., Imai, S., et al. Negative control of p53 by Sir2α promotes cell survival under stress. Cell 107 137-148 (2001).

Vaziri, H., Dessain, S.K., Eaton, E.N., et al. hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase. Cell 107 149-159 (2001).

Langley, E., Pearson, M., Faretta, M., et al. Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J 21(10) 2383-2396 (2002).

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