Nucleophosmin/B23 regulates the susceptibility of human leukemia HL-60 cells to sodium butyrate-induced apoptosis and inhibition of telomerase activity.

Stable clones of HL-60 cells in which nucleophosmin/B23 was over-expressed or down-regulated were established. The nucleophosmin/B23 protein levels in nucleophosmin/B23 over-expressed (pCR3-B23) or down-regulated (pCR3-32B) cells during BuONa/vanadate-induced apoptosis were characterized as compared with control vector-transfected (pCR3) cells. Over-expression of nucleophosmin/B23 resulted in decreased susceptibility of the cells to BuONa/vanadate-induced apoptosis. The response to inhibition of telomerase activity under BuONa/vanadate treatment also decreased in nucleophosmin/B23 over-expressed (pCR3-B23) cells. On the other hand, down-regulation of nucleophosmin/B23 made the cells more susceptible to BuONa-induced apoptosis or inhibition of telomerase activity. More precisely, by serial dilutions of each extract, the telomerase activity of the cells without drug treatment was determined and was found to be higher in nucleophosmin/B23 over-expressed (pCR3-B23) cells and lower in nucleophosmin/B23 down-regulated (pCR3-32B) cells as compared with the control vector-transfected (pCR3) cells. Our results indicate that nucleophosmin/B23 plays a functional role in the control of cellular apoptosis and immortalization.