Abstract
The Upstream Binding Factor 1 (UBF1) is a nucleolar protein that participates in the regulation of RNA polymerase I activity and ribosomal RNA (rRNA) synthesis. In 32D myeloid cells expressing the type 1 insulin-like growth factor receptor (IGF-IR), the UBF1 protein (but not its mRNA) is down regulated when the cells are shifted from Interleukin-3 (IL-3) to IGF-1. Ectopic expression of insulin receptor substrate-1 (IRS-1) in these cells inhibits the down-regulation of UBF1. We now show that the stability of UBF1 in 32D-derived cells requires also a signal from the extracellular regulated kinases (ERKs). When ERKs signaling is defective, as in cells over-expressing the insulin receptor (InR) or selected mutants of the IGF-1R, UBF1 is down-regulated, even in the presence of IRS-1. The down-regulation is corrected by the expression of an activated Ha-ras, which stimulates ERKs activity. Mutations at threonines 117 and 201 of UBF1, known to be phosphorylated by ERKs, cause its down-regulation. However, when IRS-2, instead of IRS-1, is ectopically expressed in 32D InR cells, ERKs phosphorylation is increased and UBF is stabilized. Taken together, these results indicate that in 32D-derived myeloid cells expressing either the IGF-IR or the InR, UBF1 levels are regulated by signaling from both IRS proteins and ERKs.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Butadienes / pharmacology
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Cell Line
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Down-Regulation
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / metabolism*
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Insulin / metabolism
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Insulin Receptor Substrate Proteins
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Insulin-Like Growth Factor I / metabolism
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Interleukin-3 / metabolism
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Mice
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Mutation
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Myeloid Cells / drug effects
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Myeloid Cells / metabolism*
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Nitriles / pharmacology
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Phosphorylation
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Pol1 Transcription Initiation Complex Proteins / genetics
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Pol1 Transcription Initiation Complex Proteins / metabolism*
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Protein Kinase Inhibitors / pharmacology
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Protein Processing, Post-Translational*
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Proto-Oncogene Proteins p21(ras) / genetics
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Proto-Oncogene Proteins p21(ras) / metabolism
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Receptor, IGF Type 1 / genetics
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Receptor, IGF Type 1 / metabolism*
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Receptor, Insulin / metabolism
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Signal Transduction* / drug effects
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Time Factors
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Transfection
Substances
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Butadienes
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Insulin
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Insulin Receptor Substrate Proteins
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Interleukin-3
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Intracellular Signaling Peptides and Proteins
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Irs1 protein, mouse
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Irs2 protein, mouse
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Nitriles
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Phosphoproteins
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Pol1 Transcription Initiation Complex Proteins
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Protein Kinase Inhibitors
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U 0126
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transcription factor UBF
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Insulin-Like Growth Factor I
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Receptor, IGF Type 1
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Receptor, Insulin
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Extracellular Signal-Regulated MAP Kinases
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Proto-Oncogene Proteins p21(ras)