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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2005-2-21
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pubmed:abstractText |
Sir2 is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase involved in gene silencing and longevity. Cellular stresses affect Sir2 activity, but the mechanisms of Sir2 regulation are debated. Nicotinamide has been proposed as a physiological regulator that inhibits Sir2 deacetylase activity by chemical reversal of a covalent reaction intermediate. We demonstrate a chemical strategy to activate Sir2-dependent transcriptional silencing and present evidence that the endogenous level of nicotinamide limits Sir2 activity in wild-type (wt) yeast cells. Nicotinamide inhibition of Sir2 is antagonized in vitro by isonicotinamide, which causes an increase in Sir2 deacetylation activity. Isonicotinamide also substantially increases transcriptional silencing at Sir2-regulated loci in wt strains and in strains lacking key NAD+ salvage pathway enzymes (PNC1 and NPT1). Thus, a nicotinamide antagonist is a Sir2 agonist in vitro and in vivo.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases,
http://linkedlifedata.com/resource/pubmed/chemical/NAD,
http://linkedlifedata.com/resource/pubmed/chemical/Niacinamide,
http://linkedlifedata.com/resource/pubmed/chemical/Nicotinamidase,
http://linkedlifedata.com/resource/pubmed/chemical/PNC1 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Pentosyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/SIR2 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Silent Information Regulator...,
http://linkedlifedata.com/resource/pubmed/chemical/Sirtuin 2,
http://linkedlifedata.com/resource/pubmed/chemical/Sirtuins,
http://linkedlifedata.com/resource/pubmed/chemical/isonicotinamide,
http://linkedlifedata.com/resource/pubmed/chemical/nicotinate phosphoribosyltransferase
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1097-2765
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
595-601
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15721262-Acetylation,
pubmed-meshheading:15721262-Gene Expression Regulation, Fungal,
pubmed-meshheading:15721262-Gene Silencing,
pubmed-meshheading:15721262-Histone Deacetylase Inhibitors,
pubmed-meshheading:15721262-Histone Deacetylases,
pubmed-meshheading:15721262-NAD,
pubmed-meshheading:15721262-Niacinamide,
pubmed-meshheading:15721262-Nicotinamidase,
pubmed-meshheading:15721262-Pentosyltransferases,
pubmed-meshheading:15721262-Saccharomyces cerevisiae,
pubmed-meshheading:15721262-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:15721262-Silent Information Regulator Proteins, Saccharomyces...,
pubmed-meshheading:15721262-Sirtuin 2,
pubmed-meshheading:15721262-Sirtuins,
pubmed-meshheading:15721262-Telomere,
pubmed-meshheading:15721262-Transcription, Genetic
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pubmed:year |
2005
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pubmed:articleTitle |
Chemical activation of Sir2-dependent silencing by relief of nicotinamide inhibition.
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pubmed:affiliation |
Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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