Nucleolar localization of nucleophosmin/B23 requires GTP.
Incubation of HeLa cells with the IMP dehydrogenase inhibitors: ribavirin (100 microM, 4 h), tiazofurin (100 microM, 4 h), selenazofurin (100 microM, 4 h), or mycophenolic acid (10 microM, 4 h) resulted in approximately 70% reduction in cellular GTP pools and shifting of nucleophosmin/B23 from nucleoli to nucleoplasm as detected by immunofluorescence (B23-translocation). Enzyme-linked immunosorbent assay and Western blot assay showed there is no loss or degradation of nucleophosmin/B23 protein during drug treatment. This translocation effect could be prevented by co-incubation with guanosine (100 microM) or reversed by addition of guanosine (100 microM) to the culture medium after B23-translocation had been induced by these inhibitors. Under these conditions of guanosine supplementation, cellular GTP pool concentrations were maintained at the control level. These results indicate that localization of nucleophosmin/B23 into the nucleolus is dependent on the cellular GTP level.
Finch
R A
RA
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030.
Revankar
G R
GR
Chan
P K
PK
D001692:Biological Transport; D002466:Cell Nucleolus / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D010750:Phosphoproteins / Q000378:metabolism*; D012254:Ribavirin / Q000031:analogs & derivatives / Q000494:pharmacology
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000090243:Nucleophosmin; D012254:Ribavirin; D006160:Guanosine Triphosphate; D007168:IMP Dehydrogenase