AN E-BOX ELEMENT LOCALIZED IN THE FIRST INTRON MEDIATES REGULATION OF THE PROTHYMOSIN-ALPHA GENE BY C-MYC

被引:136
作者
GAUBATZ, S [1 ]
MEICHLE, A [1 ]
EILERS, M [1 ]
机构
[1] UNIV HEIDELBERG,ZENTRUM MOLEK BIOL,D-69120 HEIDELBERG,GERMANY
关键词
D O I
10.1128/MCB.14.6.3853
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
In RAT1A fibroblasts, expression of the prothymosin alpha gene is under the transcriptional control of the c-myc proto-oncogene. We have now cloned the rat gene encoding prothymosin a and show that the cloned gene is regulated by c-myc in vivo. We find that regulation by c-myc is mediated by sequences do,vnstream of the transcriptional start site, whereas the promoter is constitutive and not regulated by c-myc. We have identified an enhancer element within the first intron that is sufficient to mediate a response to Myc and Max in transient transfection assays and to activation of estrogen receptor-Myc chimeras in vivo. We find that this element contains a consensus Myc-binding site (CACGTG). Disruption of this site abolishes the response to Myc and Max in both transient and stable assays. Mutants of either Myc or Max that are deficient for heterodimerization fail to regulate the prothymosin alpha gene, suggesting that a heterodimer between Myc and Max activates the prothymosin alpha gene. Our data define the prothymosin alpha gene as a bona fide target gene for c-myc.
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页码:3853 / 3862
页数:10
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