Nuclear transport of nicotinamide phosphoribosyltransferase is cell cycle-dependent in mammalian cells, and its inhibition slows cell growth.
3T3-L1 Cells
Acrylamides
/ pharmacology
Active Transport, Cell Nucleus
Animals
Cell Cycle Checkpoints
Cell Nucleus
/ metabolism
Cell Proliferation
Cell Survival
/ drug effects
Cytoplasm
/ metabolism
Hep G2 Cells
Histones
/ metabolism
Humans
Mice
Mutagenesis, Site-Directed
NAD
/ metabolism
Nicotinamide Phosphoribosyltransferase
/ chemistry
Oxidative Stress
Piperidines
/ pharmacology
Poly(ADP-ribose) Polymerases
/ metabolism
Recombinant Fusion Proteins
/ chemistry
Sirtuins
/ metabolism
GFP fusion
NAMPT
cancer
epigenetics
nicotinamide adenine dinucleotide (NAD)
nuclear localization
pre–B cell colony enhancing factor (PBEF)
sirtuin
visfatin
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
31 05 2019
31 05 2019
Historique:
received:
16
04
2018
revised:
04
04
2019
pubmed:
13
4
2019
medline:
19
2
2020
entrez:
13
4
2019
Statut:
ppublish
Résumé
Nicotinamide phosphoribosyltransferase (NAMPT) is located in both the nucleus and cytoplasm and has multiple biological functions including catalyzing the rate-limiting step in NAD synthesis. Moreover, up-regulated NAMPT expression has been observed in many cancers. However, the determinants and regulation of NAMPT's nuclear transport are not known. Here, we constructed a GFP-NAMPT fusion protein to study NAMPT's subcellular trafficking. We observed that in unsynchronized 3T3-L1 preadipocytes, 25% of cells had higher GFP-NAMPT fluorescence in the cytoplasm, and 62% had higher GFP-NAMPT fluorescence in the nucleus. In HepG2 hepatocytes, 6% of cells had higher GFP-NAMPT fluorescence in the cytoplasm, and 84% had higher GFP-NAMPT fluorescence in the nucleus. In both 3T3-L1 and HepG2 cells, GFP-NAMPT was excluded from the nucleus immediately after mitosis and migrated back into it as the cell cycle progressed. In HepG2 cells, endogenous, untagged NAMPT displayed similar changes with the cell cycle, and in nonmitotic cells, GFP-NAMPT accumulated in the nucleus. Similarly, genotoxic, oxidative, or dicarbonyl stress also caused nuclear NAMPT localization. These interventions also increased poly(ADP-ribosyl) polymerase and sirtuin activity, suggesting an increased cellular demand for NAD. We identified a nuclear localization signal in NAMPT and amino acid substitution in this sequence (
Identifiants
pubmed: 30975903
pii: S0021-9258(20)36387-0
doi: 10.1074/jbc.RA118.003505
pmc: PMC6552417
doi:
Substances chimiques
Acrylamides
0
Histones
0
N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide
0
Piperidines
0
Recombinant Fusion Proteins
0
NAD
0U46U6E8UK
Nicotinamide Phosphoribosyltransferase
EC 2.4.2.12
Poly(ADP-ribose) Polymerases
EC 2.4.2.30
Sirtuins
EC 3.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8676-8689Informations de copyright
© 2019 Svoboda et al.
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