title: The NAD+ synthesis enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT1) regulates ribosomal RNA transcription.
abstract: The chromosomal region encoding the nuclear NAD(+) synthesis enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT1) is frequently deleted in human cancer. We describe evidence that NMNAT1 interacts with the nucleolar repressor protein nucleomethylin and is involved in regulating rRNA transcription. NMNAT1 binds to nucleomethylin and is recruited into a ternary complex containing the NAD(+)-dependent deacetylase SirT1. NMNAT1 expression stimulates the deacetylase function of SirT1. Knockdown of NMNAT1 enhances rRNA transcription and promotes cell death after nutrient deprivation. Furthermore, NMNAT1 expression is induced by DNA damage and plays a role in preventing cell death after damage. Heterozygous deletion of NMNAT1 in lung tumor cell lines correlates with low expression level and increased sensitivity to DNA damage. These results suggest that NMNAT1 deletion in tumors may contribute to transformation by increasing rRNA synthesis, but may also increase sensitivity to nutrient stress and DNA damage.
authors.affiliation: From the Departments of Molecular Oncology and.
authors.forename: Tanjing
authors.initials: T
authors.lastname: Song
authors.affiliation: From the Departments of Molecular Oncology and.
authors.forename: Leixiang
authors.initials: L
authors.lastname: Yang
authors.affiliation: From the Departments of Molecular Oncology and.
authors.forename: Neha
authors.initials: N
authors.lastname: Kabra
authors.affiliation: From the Departments of Molecular Oncology and.
authors.forename: Lihong
authors.initials: L
authors.lastname: Chen
authors.affiliation: From the Departments of Molecular Oncology and.
authors.forename: John
authors.initials: J
authors.lastname: Koomen
authors.affiliation: Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida 33612.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Haura
authors.affiliation: From the Departments of Molecular Oncology and. Electronic address: jiandong.chen@moffitt.org.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Chen
mesh_terms: D000107:Acetylation / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D020868:Gene Silencing / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D008780:Methyltransferases / Q000378:metabolism; D009243:NAD / Q000096:biosynthesis*; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D012335:RNA, Ribosomal / Q000096:biosynthesis / Q000235:genetics*; D016601:RNA-Binding Proteins; D056564:Sirtuin 1 / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D009687:Nuclear Proteins; D012335:RNA, Ribosomal; D016601:RNA-Binding Proteins; D009243:NAD; D004317:Doxorubicin; D008780:Methyltransferases; C529371:RRP8 protein, human; C484007:NMNAT1 protein, human; D009612:Nicotinamide-Nucleotide Adenylyltransferase; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D005947:Glucose
keywords: Glucose; Glucose Deprivation; NAD; NML; NMNAT1; Nucleolus; Ribosomal RNA (rRNA); Sirt1