c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription.
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 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.
Arabi
Azadeh
A
Södertörns Högskola, S-141 89 Huddinge, Sweden. azadeh.arabi@sh.se
Wu
Siqin
S
Ridderstråle
Karin
K
Bierhoff
Holger
H
Shiue
Chiounan
C
Fatyol
Karoly
K
Fahlén
Sara
S
Hydbring
Per
P
Söderberg
Ola
O
Grummt
Ingrid
I
Larsson
Lars-Gunnar
LG
Wright
Anthony P H
AP
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D004275:DNA, Ribosomal / Q000737:chemistry* / Q000378:metabolism; D015536:Down-Regulation; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008024:Ligands; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism / Q000502:physiology*; D012318:RNA Polymerase I / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013696:Temperature; D014158:Transcription, Genetic
D004275:DNA, Ribosomal; D006657:Histones; D008024:Ligands; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D012318:RNA Polymerase I; D046988:Proteasome Endopeptidase Complex