2005
DOI: 10.1038/ncb1225
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c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription

Abstract: The c-Myc oncoprotein regulates transcription of genes that are associated with cell growth, proliferation and apoptosis. c-Myc levels are modulated by ubiquitin/proteasome-mediated degradation. Proteasome inhibition leads to c-Myc accumulation within nucleoli, indicating that c-Myc might have a nucleolar function. Here we show that the proteins c-Myc and Max interact in nucleoli and are associated with ribosomal DNA. This association is increased upon activation of quiescent cells and is followed by recruitme… Show more

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Cited by 433 publications
(394 citation statements)
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“…Our results showing reduced RNA synthesis in human T cells treated with the OGT inhibitor (Fig. 7) are fully consistent with decreased c-myc expression, because c-myc activates transcription of rRNA (88,89), and a large fraction of the labeled RNA likely represents rRNA based on its nucleolar staining pattern. Although c-myc is undoubtedly one important OGT substrate, we identified hundreds of other potentially relevant substrates (Supplemental Table I).…”
Section: Discussionsupporting
confidence: 82%
“…Our results showing reduced RNA synthesis in human T cells treated with the OGT inhibitor (Fig. 7) are fully consistent with decreased c-myc expression, because c-myc activates transcription of rRNA (88,89), and a large fraction of the labeled RNA likely represents rRNA based on its nucleolar staining pattern. Although c-myc is undoubtedly one important OGT substrate, we identified hundreds of other potentially relevant substrates (Supplemental Table I).…”
Section: Discussionsupporting
confidence: 82%
“…This hyperacetylation of histones was linked to transcription activation (Nourani et al, 2001) and NuA4-dependent acetylation of histone H4 was shown to affect transcription of specific genes such as His4, Lys2 (Galarneau et al, 2000), ribosomal proteins and heat-shock proteins (Reid et al, 2000). Arabi et al (2005) have shown that TRRAP is recruited by c-Myc to the promoters of Pol I transcribed genes. The recruitment of TRRAP leads to an increased histone aceylation, followed by recruitment of RNA polymerase I and activation of rDNA transcription.…”
Section: Transcriptionmentioning
confidence: 99%
“…Insulin and IGF-1 stimulate the activity of polymerase I transcription by elevating both UBF protein level and phosphorylation (Hannan et al, 1998;Wu et al, 2005). Partial hepatectomy induces a progressive increase in rRNA synthesis (up to 24 h after operation) in regenerating rat hepatocytes (Sirri et al, 1995) very likely due to the induction of c-myc (Thompson et al, 1986), which controls the RNA polymerase I activity (Arabi et al, 2005;Grandori et al, 2005;Grewal et al, 2005). Cortisol at the dose used in the present experiments stimulated rRNA transcription in rat hepatocytes (Sirri et al, 1995) by activating the glycocorticoid receptor signalling (Glibetic et al, 1993), while inhibiting their proliferation (Nadal, 1995).…”
Section: Polr1a Silencing Stabilises P53 Without Disrupting the Nuclementioning
confidence: 99%