A role for c-Myc in the regulation of ribosomal RNA processing

被引:156
|
作者
Schlosser, I
Hölzel, M
Mürnseer, M
Burtscher, H
Weidle, UH
Eick, D
机构
[1] GSF, Natl Res Ctr Environm & Hlth, Inst Clin Mol Biol & Tumor Genet, D-81377 Munich, Germany
[2] Roche Diagnost GmbH, Dept TRON, D-82372 Penzberg, Germany
关键词
D O I
10.1093/nar/gkg794
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 proto-oncogene c-myc encodes a basic helix-loop-helix leucine zipper transcription factor (c-Myc) that has a profound role in growth control and cell cycle progression. Previous microarray studies identified various classes of c-Myc target genes, including genes involved in ribosome biogenesis. By screening the human B-cell line P493-6 and rat fibroblasts conditionally expressing c-Myc, we could substantially extend the list of c-Myc target genes, particularly those required for ribosome biogenesis. The identification of 38 new c-Myc target genes with nucleolar function, prompted us to investigate processing of ribosomal RNA (rRNA). Using pulse-chase labelling experiments we show that c-Myc regulates the efficiency of rRNA maturation. In serum-stimulated P493-6 cells, only the processing of the 47S rRNA precursor to mature 18S and 28S rRNA, but not the synthesis of the 47S transcript, was dependent on the presence of c-Myc. As processing of rRNA is sensitive to inhibition of cyclin-dependent kinase (cdk) activity by roscovitine, we conclude that c-Myc regulates cell growth and proliferation by the coordinated induction of cdk activity and rRNA processing.
引用
收藏
页码:6148 / 6156
页数:9
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