Regulation of Nucleophosmin/B23 during Retinoic Acid-induced HL-60 Cell Differentiation

• Main Authors: Kang Hong Tzeng, 曾凱鴻
• Other Authors: Yat Ming Yung
• Format: Others
• Language: en_US
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/86233161864917689968

碩士 === 長庚大學 === 基礎醫學研究所 === 93 === The biological effects, involved in cell and developmental biology, nutrition, and cancer chemotherapy, of retinoic acid (RA) have been well studied. RA is already known as a potent inducer of leukemia cell differentiation and growth arrest, but its molecular mechanisms are not fully defined. Nucleophosmin/B23 is a multifunctional nucleolar phosphoprotein. It plays critical roles in the control of centrosome duplication, cell cycle progression, cell proliferation, cell apoptosis, cell differentiation, and transcriptional regulation. Whether B23 is a key molecule involved in regulating the susceptibility of tumor cells to chemotherapeutics of cell differentiation becomes an important question to be addressed. Our previous experiments have shown that B23, c-Myc, and YY1 are down-regulated during RA-induced HL-60 cell differentiation. In this study, attempts were further to elucidate the detailed mechanism of RA-mediated repression of B23, and the role of B23 during RA-induced HL-60 cell differentiation. The results exhibited that the B23 promoter activity depends on intact YY1 and dual c-Myc binding sites, and mutation of these binding sites can abolish the B23 promoter activity. RA inhibits the expression of B23 by down-regulation of YY1 and c-Myc activities during cell differentiation. Moreover, the regulatory complex is formed with AP-2α and B23 in HL-60 cells, and targeted to the AP-2α binding sites in the promoters of RA-responsive gene, including B23. The bindings of the complex containing AP-2α and B23 to the RA-repressed genes are enhanced by RA treatment. These evidences suggest that B23 can involve in the transcriptional regulation by associating with transcription factors.