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- W2045442669 abstract "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(+)." @default.
- W2045442669 created "2016-06-24" @default.
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- W2045442669 date "2009-07-01" @default.
- W2045442669 modified "2023-10-16" @default.
- W2045442669 title "Enzymes in the NAD+ Salvage Pathway Regulate SIRT1 Activity at Target Gene Promoters" @default.
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- W2045442669 doi "https://doi.org/10.1074/jbc.m109.016469" @default.
- W2045442669 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2740465" @default.
- W2045442669 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19478080" @default.
- W2045442669 hasPublicationYear "2009" @default.
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