Reduced level of ATF is correlated with transcriptional repression of DNA topoisomerase IIα gene during TPA‐induced differentiation of HL‐60 cells

DNA topoisomerase II is a marker for the proliferation state of mammalian cells in culture, and the protein levels are markedly higher in exponentially growing cells than quiescent cells and can be downregulated by growth of the cells at high density and serum starvation. Correlation between ATF and TPA-repressed DNA topoisomerase IIα (Topo IIα) mRNA has been investigated during TPA-induced differentiation of HL-60 cells. Topo IIα RNA and unknotting activity were reduced at 24 hours in TPA-treated HL-60 cells. The level of Topo IIα mRNA and the activity were gradually decreased in proportion to the concentration of TPA. Two DNA-protein complexes were formed by DNA mobility shift assay when ATF-binding site was incubated with nuclear extract prepared from TPA-free HL-60 cells, and the amount of ATF was vanished after TPA treatment. TPA-repressed Topo IIα mRNA and ATF levels were partially restored after pretreatment of staurosporin. These results suggest that the reduced level of ATF may be important to the transcriptional repression of Topo IIα gene during TPA-induced differentiation in HL-60 cells and related to protein kinase C signal pathway.