Abstract
The retinoic acid-induced differentiation of human leukemia HL-60 cells towards mature granulocytic cells was accompanied by the decline in the protein levels of c-myc, nucleophosmin/B23 and its promoter activity. These RA-induced effects were further enhanced by the concurrent treatment of HL-60 cells with p38 map kinase inhibitor SB203580 (SB). It seems that there is a strong correlation of nucleophosmin/B23 and c-Myc expressions in cells under RA treatment. Furthermore, nucleophosmin/B23 promoter activity decreased upon c-Myc antisense-mediated reduction of intracellular amount of c-Myc. CHIP assays showed that binding of c-Myc to the nucleophosmin/B23 promoter decreased in RA-treated cells. Thus, nucleophosmin/B23 expression is targeted by c-Myc during RA-induced differentiation. These results provide evidence for a novel mechanism of transcriptional downregulation of nucleophosmin/B23 and the functional role of c-Myc in RA-induced differentiation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal / metabolism
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Blotting, Western
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Cell Differentiation / drug effects*
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Chromatin Immunoprecipitation
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Down-Regulation / drug effects
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Enzyme Inhibitors / pharmacology
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Fluorescein-5-isothiocyanate
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Fluorescent Dyes
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Gene Expression Regulation, Neoplastic / drug effects*
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HL-60 Cells
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Humans
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Imidazoles / pharmacology
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Nuclear Proteins / metabolism*
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Nucleophosmin
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Oligonucleotides, Antisense / pharmacology
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Phosphoproteins / metabolism
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Promoter Regions, Genetic
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Proto-Oncogene Proteins c-myc / metabolism*
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Pyridines / pharmacology
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Temperature
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Time Factors
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Transcription, Genetic / drug effects
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Tretinoin / pharmacology*
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p38 Mitogen-Activated Protein Kinases / drug effects
Substances
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Antibodies, Monoclonal
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Enzyme Inhibitors
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Fluorescent Dyes
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Imidazoles
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NPM1 protein, human
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Nuclear Proteins
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Oligonucleotides, Antisense
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Phosphoproteins
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Proto-Oncogene Proteins c-myc
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Pyridines
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Nucleophosmin
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Tretinoin
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p38 Mitogen-Activated Protein Kinases
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Fluorescein-5-isothiocyanate
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SB 203580