Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity.
The yeast Sir2 protein regulates epigenetic gene silencing and as a possible antiaging effect it suppresses recombination of rDNA. Studies involving cobB, a bacterial SIR2-like gene, have suggested it could encode a pyridine nucleotide transferase. Here five human sirtuin cDNAs are characterized. The SIRT1 sequence has the closest homology to the S. cerevisiae Sir2p. The SIRT4 and SIRT5 sirtuins more closely resemble prokaryotic sirtuin sequences. The five human sirtuins are widely expressed in fetal and adult tissues. Recombinant E. coli cobT and cobB proteins each showed a weak NAD-dependent mono-ADP-ribosyltransferase activity using 5, 6-dimethylbenzimidazole as a substrate. Recombinant E. coli cobB and human SIRT2 sirtuin proteins were able to cause radioactivity to be transferred from [32P]NAD to bovine serum albumin (BSA). When a conserved histidine within the human SIRT2 sirtuin was converted to a tyrosine, the mutant recombinant protein was unable to transfer radioactivity from [32P]NAD to BSA. These results suggest that the sirtuins may function via mono-ADP-ribosylation of proteins.
Frye
R A
RA
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, 15240, USA. frye01@pitt.edu
D036002:ADP Ribose Transferases; D000595:Amino Acid Sequence; D018076:DNA, Complementary / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D006655:Histone Deacetylases; D006801:Humans; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D009713:Nucleotidyltransferases; D010430:Pentosyltransferases / Q000737:chemistry; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D012710:Serum Albumin, Bovine / Q000378:metabolism; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins; D014018:Tissue Distribution; D015534:Trans-Activators / Q000737:chemistry*
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009097:Multienzyme Complexes; D011994:Recombinant Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D015534:Trans-Activators; D012710:Serum Albumin, Bovine; D036002:ADP Ribose Transferases; D010430:Pentosyltransferases; C028015:nicotinate-nucleotide-dimethylbenzimidazole phosphoribosyltransferase; D011065:Poly(ADP-ribose) Polymerases; D009713:Nucleotidyltransferases; C087778:SIR2 protein, S cerevisiae; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases