Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocytes
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Cell Cycle
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Cell Line
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Cell Nucleolus / drug effects
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Cell Nucleolus / genetics
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Cyclin-Dependent Kinases / antagonists & inhibitors
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Cyclin-Dependent Kinases / metabolism
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Fibroblasts
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Humans
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Kinetics
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Mitogens / pharmacology
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Models, Genetic
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Oligonucleotide Array Sequence Analysis
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Proto-Oncogene Mas
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism*
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Purines / pharmacology
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RNA Polymerase I / metabolism
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RNA Precursors / chemistry
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RNA Precursors / genetics
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RNA Precursors / metabolism*
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RNA Processing, Post-Transcriptional* / drug effects
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RNA, Ribosomal / biosynthesis
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RNA, Ribosomal / chemistry
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RNA, Ribosomal / genetics
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RNA, Ribosomal / metabolism*
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RNA, Ribosomal, 18S / biosynthesis
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RNA, Ribosomal, 18S / chemistry
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RNA, Ribosomal, 18S / genetics
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RNA, Ribosomal, 18S / metabolism
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RNA, Ribosomal, 28S / biosynthesis
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RNA, Ribosomal, 28S / chemistry
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RNA, Ribosomal, 28S / genetics
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RNA, Ribosomal, 28S / metabolism
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Rats
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Ribosomes / drug effects
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Ribosomes / genetics
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Ribosomes / metabolism
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Roscovitine
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Substrate Specificity
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Transcription, Genetic / genetics
Substances
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MAS1 protein, human
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Mitogens
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Proto-Oncogene Mas
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Proto-Oncogene Proteins c-myc
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Purines
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RNA Precursors
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RNA, Ribosomal
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RNA, Ribosomal, 18S
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RNA, Ribosomal, 28S
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Roscovitine
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Cyclin-Dependent Kinases
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RNA Polymerase I