Myc induces the nucleolin and BN51 genes: possible implications in ribosome biogenesis

被引:108
作者
Greasley, PJ
Bonnard, C
Amati, B
机构
[1] Swiss Inst Expt Canc Res, Cellular Growth Control Unit, CH-1066 Epalinges, Switzerland
[2] Swiss Inst Expt Canc Res, Biocomp Unit, CH-1066 Epalinges, Switzerland
关键词
D O I
10.1093/nar/28.2.446
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
The c-Myc oncoprotein and its dimerization partner Max bind the DNA core consensus sequence CACGTG (E-box) and activate gene transcription. However, the low levels of induction have hindered the identification of novel Myc target genes by differential screening techniques, Here, we describe a computer-based pre-selection of candidate Myc/Max target genes, based on two restrictive criteria: an extended E-box consensus sequence for Myc/Max binding and the occurrence of this sequence within a potential genomic CpG island. Candidate genes selected by these criteria were evaluated experimentally for their response to Myc. Two Myc target genes are characterized here in detail. These encode nucleolin, an abundant nucleolar protein, and BN51, a co-factor of RNA polymerase III. Myc activates transcription of both genes via E-boxes located in their first introns, as seen for several well-characterized Myc targets, For both genes, mutation of the E-boxes abolishes transcriptional activation by Myc as well as repression by Mad1. In addition, the BN51 promoter is selectively activated by Myc and not by USF, another E-box-binding factor, Both nucleolin and BN51 are implicated in the maturation of ribosomal RNAs, albeit in different ways. We propose that Myc, via regulation of these and probably many other transcriptional targets, may be an important regulator of ribosome biogenesis.
引用
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页码:446 / 453
页数:8
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