GABP complex regulates transcription of eIF6 (p27BBP), an essential trans-acting factor in ribosome biogenesis.
Eukaryotic initiation factor 6 (eIF6, alias p27BBP) is required for the biogenesis of 60S ribosomal subunits. eIF6 expression levels are tightly regulated in vivo, where they correlate with cellular growth. We analyzed how transcriptional regulation of eIF6 is achieved. We show that the human eIF6 promoter contains consensus sites for the GABP (GA-binding protein) transcription factor complex. Functional analysis of GABP consensus sequences by point mutations, EMSA (electrophoretic mobility shift assay) and a dominant negative mutant indicates that GABP is essential for eIF6 promoter activity. These data strengthen the hypothesis that GABP is a global regulator of ribosome synthesis.
Donadini
Alessandra
A
San Raffaele Scientific Institute, 20132 Milan, Italy.
Giacopelli
Francesca
F
Ravazzolo
Roberto
R
Gandin
Valentina
V
Marchisio
Pier Carlo
PC
Biffo
Stefano
S
D002352:Carrier Proteins / Q000235:genetics*; D002466:Cell Nucleolus / Q000378:metabolism; D016384:Consensus Sequence / Q000235:genetics; D019281:Dimerization; D039642:Eukaryotic Initiation Factors; D051268:GA-Binding Protein Transcription Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012270:Ribosomes / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic
D002352:Carrier Proteins; C109284:EIF6 protein, human; D039642:Eukaryotic Initiation Factors; D051268:GA-Binding Protein Transcription Factor; D007381:Intermediate Filament Proteins; D015534:Trans-Activators