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The NAD+ Synthesis Enzyme Nicotinamide Mononucleotide Adenylyltransferase (NMNAT1) Regulates Ribosomal RNA Transcription*
- Publication Year :
- 2013
- Publisher :
- American Society for Biochemistry and Molecular Biology, 2013.
-
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.
- Subjects :
- Transcription, Genetic
DNA damage
Gene Dosage
Repressor
Down-Regulation
Biochemistry
Sirtuin 1
Transcription (biology)
NMNAT1
Cell Line, Tumor
Humans
Gene Regulation
Gene Silencing
Nicotinamide-Nucleotide Adenylyltransferase
Molecular Biology
Nicotinamide-nucleotide adenylyltransferase
biology
Cell Death
Nuclear Proteins
RNA-Binding Proteins
Acetylation
Cell Biology
Methyltransferases
NAD
Molecular biology
RRNA transcription
Gene Expression Regulation, Neoplastic
Glucose
Doxorubicin
RNA, Ribosomal
Gene Knockdown Techniques
biology.protein
NAD+ kinase
Cell Nucleolus
DNA Damage
Protein Binding
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....1cc2fa3b5861c486ffb48be7f4ea8fdc