REDUCED LEVEL OF ATF IS CORRELATED WITH TRANSCRIPTIONAL REPRESSION OFDNA TOPOISOMERASE II-ALPHA GENE DURING TPA-INDUCED DIFFERENTIATION OFHL-60 CELLS

DNA topoisomerase II is a marker for the proliferation state of mammal ian cells in culture, and the protein levels are markedly higher in ex ponentially growing cells than quiescent cells and can be downregulate d by growth of the cells at high density and serum starvation. Correla tion between ATF and TPA-repressed DNA topoisomerase II alpha (Topo II alpha) mRNA has been investigated during TPA-induced differentiation of HL-60 cells. Topo II alpha mRNA and unknotting activity were reduce d at 24 hours in TPA-treated HL-60 cells. The level of Topo II alpha m RNA and the activity were gradually decreased in proportion to the con centration of TPA. Two DNA-protein complexes were formed by DNA mobili ty shift assay when ATF-binding site was incubated with nuclear extrac t prepared from TPA-free HL-60 cells, and the amount of ATF was vanish ed after TPA treatment. TPA-repressed Topo II alpha mRNA and ATF level s were partially restored after pretreatment of staurosporin. These re sults suggest that the reduced level of ATF may be important to the tr anscriptional repression of Topo II alpha gene during TPA-induced diff erentiation in HL-60 cells and related to protein kinase C signal path way.