MAZ, a Myc-associated zinc finger protein, is essential for the ME1a1-mediated expression of the c-myc gene during neuroectodermal differentiation of P19 cells

被引:35
作者
Komatsu, M
Li, HO
Tsutsui, H
Itakura, K
Matsumura, M
Yokoyama, KK
机构
[1] RIKEN, TSUKUBA LIFE SCI CTR, TSUKUBA, IBARAKI 305, JAPAN
[2] CITY HOPE NATL MED CTR, BECKMAN RES INST, DEPT MOL GENET, DUARTE, CA 91010 USA
[3] UNIV TSUKUBA, INST APPL BIOCHEM, TSUKUBA, IBARAKI 305, JAPAN
基金
日本科学技术振兴机构;
关键词
MAZ; c-myc; ME1a1; site; gene expression;
D O I
10.1038/sj.onc.1201283
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To investigate whether MAZ (Myc-associated zinc finger protein) affects the expression of the c-myc gene during the retinoic acid-induced (RA-induced) neuroectodermal differentiation of P19 embryonal carcinoma (EC) cells, we introduced a CAT reporter construct, human c-myc promoter/CAT (pMyc2CAT), and a mutant CAT derivative that lacked an ME1a1 site (pMyc1CAT) into P19EC cells tp monitor the promoter activity of the c-myc gene, The expression of CAT in pMyc2CAT-transformed cells declined fivefold after 24 h in the presence of RA, returned to the normal level within 48 h, and decreased again to below 20% of the normal level after 96 h. By contrast, the expression of CAT in pMyc1CAT-transformed cells did not return to the normal level after 48 h in the presence of RA, In addition, an electrophoretic mobility shift assay (EMSA) with ME1a1 DNA as probe demonstrated that the kinetics of the DNA-binding activity of MAZ were closely correlated with the changes in the expression of CAT from the c-myc promoter/CAT gene during the differentiation of P19EC cells, Taken together, these results suggest that MAZ plays a key role in the transient increase in the expression of the c-myc gene after 48 h of exposure to RA during the neuroectodermal differentiation of P19EC cells.
引用
收藏
页码:1123 / 1131
页数:9
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