c-myc activates RCC1 gene expression through E-box elements

Oncogene
M TsuneokaE Mekada

Abstract

Proto-oncogene c-myc is implicated in proliferation of mammalian cells. Although c-Myc protein has been demonstrated to function as a transcription factor recognizing an E-box (CACGTG) element, few c-myc-regulated genes have been identified and the specific role of c-myc is still unclear. RCC1 is necessary for mammalian cells to proliferate. Four CACGTG elements exist within 1.3 kb downstream of the major transcription start site for the human RCC1 gene in HeLa cells. Stimulation of HeLa cells with serum increased c-myc expression and RCC1 expression. Therefore the relationship between the expression of RCC1 and c-myc was investigated. Rat 3Y1 cells overexpressing c-myc contained about twice as much RCC1 mRNA as control cells. When a chimeric protein comprised of c-myc and the estrogen binding domain of estrogen receptor was activated by addition of 4-hydroxytamoxifen (OHT), expression of RCC1 mRNA increased twofold. To examine whether c-Myc functions through the CACGTG elements, a DNA fragment of RCC1 intron 4, exon 5 and part of intron 5 was joined to firefly luciferase cDNA to construct a reporter plasmid. In transient expression experiments using HeLa cells, co-transfection with c-myc stimulated the luciferase activity up t...Continue Reading

Citations

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