An immediate response of ribosomal transcription to growth factor stimulation in mammals is mediated by ERK phosphorylation of UBF.
Ribosomal transcription in mammals is regulated in response to growth, differentiation, disease, and aging, but the mechanisms of this regulation have remained unresolved. We show that epidermal growth factor induces immediate, ERK1/2-dependent activation of endogenous ribosomal transcription, while inactivation of ERK1/2 causes an equally immediate reversion to the basal transcription level. ERK1/2 was found to phosphorylate the architectural transcription factor UBF at amino acids 117 and 201 within HMG boxes 1 and 2, preventing their interaction with DNA. Mutation of these sites inhibited transcription activation and abrogated the transcriptional response to ERK1/2. Thus, growth factor regulation of ribosomal transcription likely acts by a cyclic modulation of DNA architecture. The data suggest a central role for ribosome biogenesis in growth regulation.
Stefanovsky
V Y
VY
Cancer Research Centre and Department of Medical Biology, Laval University, Hôtel-Dieu de Québec, 11 côte du Palais, G1R 2J6, Québec, Canada.
Pelletier
G
G
Hannan
R
R
Gagnon-Kugler
T
T
Rothblum
L I
LI
Moss
T
T
D000818:Animals; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009154:Mutation; D010766:Phosphorylation; D035463:Pol1 Transcription Initiation Complex Proteins; D017433:Protein Structure, Secondary; D012318:RNA Polymerase I / Q000378:metabolism; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*
D004268:DNA-Binding Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; D012335:RNA, Ribosomal; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C063844:transcription factor UBF; D004815:Epidermal Growth Factor; D004247:DNA; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D012318:RNA Polymerase I