Regulation of upstream binding factor 1 activity by insulin-like growth factor I receptor signaling.
The upstream binding factor 1 (UBF1) is one of the proteins in a complex that regulates the activity of RNA polymerase I, which controls the rate of ribosomal RNA (rRNA) synthesis. We have shown previously that insulin receptor substrate-1 (IRS-1) can translocate to the nuclei and nucleoli of cells and bind UBF1. We report here that activation of the type I insulin-like growth factor receptor (IGF-IR) by IGF-I increases transcription from the ribosomal DNA (rDNA) promoter in both myeloid cells and mouse fibroblasts. The increased activity of the rDNA promoter is accompanied by increased phosphorylation of UBF1, a requirement for UBF1 activation. Phosphorylation occurs on a number of UBF1 peptides, most prominently on the highly acidic, serine-rich C terminus. In myeloid cells (but not in mouse embryo fibroblasts) IRS-1 signaling stabilizes the levels of UBF1 protein. These findings demonstrate that IGF-IR signaling can increase the activity of UBF1 and transcription from the rDNA promoter, providing one explanation for the reported effects of the IGF/IRS-1 axis on cell and body size in animals and cells in culture.
Wu
An
A
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Tu
Xiao
X
Prisco
Marco
M
Baserga
Renato
R
D016475:3T3 Cells; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002454:Cell Differentiation; D002466:Cell Nucleolus / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004275:DNA, Ribosomal / Q000737:chemistry / Q000378:metabolism; D005091:Exons; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009154:Mutation; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000737:chemistry; D035463:Pol1 Transcription Initiation Complex Proteins / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D012335:RNA, Ribosomal / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D014357:Trypsin / Q000494:pharmacology
D004275:DNA, Ribosomal; D010455:Peptides; D035463:Pol1 Transcription Initiation Complex Proteins; D012333:RNA, Messenger; D012335:RNA, Ribosomal; C063844:transcription factor UBF; D019000:Phosphotyrosine; D017526:Receptor, IGF Type 1; D014357:Trypsin