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.

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