Reduced level of ATF is correlated with transcriptional repression of DNA topoisomerase II alpha 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 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 reduced at 24 hours in TPA-treated HL-60 cells. The level of Topo II alpha 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 II alpha 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 II alpha gene during TPA-induced differentiation in HL-60 cells and related to protein kinase C signal pathway.
Department of Biochemistry and Surgery, College of Medicine, Chungnam National University, Daejeon, Korea. kyulim@hanbat.chungnam.ac.kr
K
K
Lim
J I
JI
Lee
K A
KA
Yun
M Y
MY
Son
J I
JI
Park
W H
WH
Yoon
B D
BD
Hwang
D051696:Activating Transcription Factors; D000951:Antigens, Neoplasm; D001665:Binding Sites; D001798:Blood Proteins / Q000378:metabolism*; D015152:Blotting, Northern; D002454:Cell Differentiation; D004247:DNA / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis / Q000235:genetics*; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004794:Enzyme Repression / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D051696:Activating Transcription Factors; D000951:Antigens, Neoplasm; D001798:Blood Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA; D011493:Protein Kinase C; D004250:DNA Topoisomerases, Type II; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate