http://purl.uniprot.org/citations/19478080 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/19478080 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/19478080 | http://www.w3.org/2000/01/rdf-schema#comment | "In mammals, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 1 (NMNAT-1) constitute a nuclear NAD(+) salvage pathway which regulates the functions of NAD(+)-dependent enzymes such as the protein deacetylase SIRT1. One of the major functions of SIRT1 is to regulate target gene transcription through modification of chromatin-associated proteins. However, little is known about the molecular mechanisms by which NAD(+) biosynthetic enzymes regulate SIRT1 activity to control gene transcription in the nucleus. In this study we show that stable short hairpin RNA-mediated knockdown of NAMPT or NMNAT-1 in MCF-7 breast cancer cells reduces total cellular NAD(+) levels and alters global patterns of gene expression. Furthermore, we show that SIRT1 plays a key role in mediating the gene regulatory effects of NAMPT and NMNAT-1. Specifically, we found that SIRT1 binds to the promoters of genes commonly regulated by NAMPT, NMNAT-1, and SIRT1 and that SIRT1 histone deacetylase activity is regulated by NAMPT and NMNAT-1 at these promoters. Most significantly, NMNAT-1 interacts with, and is recruited to target gene promoters by SIRT1. Collectively, our results reveal a mechanism for the direct control of SIRT1 deacetylase activity at a set of target gene promoters by NMNAT-1. This mechanism, in collaboration with NAMPT-dependent regulation of nuclear NAD(+) production, establishes an important pathway for transcription regulation by NAD(+)."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m109.016469"xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m109.016469"xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/author | "Zhang T."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/author | "Zhang T."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/author | "Yang T."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/author | "Yang T."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/author | "Sauve A.A."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/author | "Sauve A.A."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/author | "Krishnakumar R."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/author | "Krishnakumar R."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/author | "Kraus W.L."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/author | "Kraus W.L."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/author | "Gamble M.J."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/author | "Gamble M.J."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/author | "Berrocal J.G."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/author | "Berrocal J.G."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/author | "DuMond M.E."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/author | "DuMond M.E."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/author | "Frizzell K.M."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/author | "Frizzell K.M."xsd:string |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
http://purl.uniprot.org/citations/19478080 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |