Increased stability of nucleophosmin/B23 in anti-apoptotic effect of ras during serum deprivation.
We obtained evidence that increased stability of nucleophosmin/B23 is involved in antiapoptotic effect of ras during serum deprivation. Nucleophosmin/B23 in serum-deprived (0% serum) NIH-3T3 cells was found to be highly unstable with a half-life less than 4 h. In contrast, nucleophosmin/B23 in serum-deprived ras-transformed (RAS-3T3) cells was as stable as that in serum-supplemented NIH-3T3 or RAS-3T3 cells. Treatment of RAS-3T3 cells with nucleophosmin/B23 antisense oligomer significantly potentiated the apoptosis induced by serum deprivation. Much less caspase-3 activity was noted in the lysate derived from serum-deprived RAS-3T3 cells compared with that in the lysate of serum-deprived NIH-3T3 cells. Cell permeable caspase-3 inhibitor added in the medium blocked the decrease of nucleophosmin/B23 and apoptosis induced by serum deprivation in NIH-3T3 cells. The inhibitor, on the other hand, promoted significant decrease of nucleolin/C23 in NIH-3T3 cells during serum deprivation. Unlike nucleolin/C23, down-regulation of nucleophosmin/B23 was thus not proliferation-dependent but caspase-3- and apoptosis-dependent. Our results indicate important relationships among ras, nucleophosmin/B23, activation of caspase-3, and induction of apoptosis.
Chou
C C
CC
Graduate Institute of Pharmacology, National Yang Ming University, Taiwan, Republic of China.
Yung
B Y
BY
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000090243:Nucleophosmin; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D018631:ras Proteins / Q000502:physiology*
D061945:Caspase Inhibitors; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; C000715570:Npm1 protein, mouse; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D000090243:Nucleophosmin; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1; D018631:ras Proteins