Nature Cell Biology7, 303 - 310 (2005)
Published online: 20 February 2005; | doi:10.1038/ncb1225
c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription
Azadeh Arabi1, 2, Siqin Wu3, Karin Ridderstråle3, Holger Bierhoff4, Chiounan Shiue1, 2, Karoly Fatyol4, Sara Fahlén3, Per Hydbring3, Ola Söderberg5, Ingrid Grummt4, Lars-Gunnar Larsson3, 6
& Anthony P. H. Wright1, 2, 6
1
Södertörns Högskola, S-141 89 Huddinge, Sweden.
2
Department of Biosciences, Karolinska Institute, S-141 57 Huddinge, Sweden.
3
Department of Plant Biology and Forest Genetics, Swedish University of Agricultural Sciences, S-750 07 Uppsala, Sweden.
4
Division of Molecular Biology of the Cell II, German Cancer Research Center, 69120 Heidelberg, Germany.
5
Department of Genetics and Pathology, The Rudbeck Laboratory, University of Uppsala, S-751 85 Uppsala, Sweden.
The c-Myc oncoprotein regulates transcription of genes that are associated with cell growth, proliferation and apoptosis1. c-Myc levels are modulated by ubiquitin/proteasome-mediated degradation1. Proteasome inhibition leads to c-Myc accumulation within nucleoli2, 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 recruitment of the Myc cofactor TRRAP, enhanced histone acetylation, recruitment of RNA polymerase I (Pol I), and activation of rDNA transcription. Using small interfering RNAs (siRNAs) against c-Myc and an inhibitor of Myc−Max interactions, we demonstrate that c-Myc is required for activating rDNA transcription in response to mitogenic signals. Furthermore, using the ligand-activated MycER (ER, oestrogen receptor) system, we show that c-Myc can activate Pol I transcription in the absence of Pol II transcription. These results suggest that c-Myc coordinates the activity of all three nuclear RNA polymerases, and thereby plays a key role in regulating ribosome biogenesis and cell growth.
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