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Multiple growth factor induction of a murine early response gene that complements a lethal defect in yeast ribosome
S A Nelson1, J P Aris, B K Patel
1Laboratory of Cellular and Molecular Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA.
Abstract:
Identification of the transcriptionally activated targets of receptor tyrosine kinases is critical to understanding biologic programs directing both normal and neoplastic growth. To elucidate these molecular processes, we identified genes induced by a potent mesenchymal mitogen, platelet-derived growth factor (PDGF). Using differential display reverse transcription-polymerase chain reaction technology, we isolated a novel growth factor-induced cDNA, San5. San5 transcript induction occurred within 60 min in NIH 3T3 fibroblasts and proceeded in the presence of cycloheximide. Maximal induction of the San5 transcript occurred between 8 and 16 h, concurrent with passage of fibroblasts through G(1). San5 message was potently induced by PDGF AA and BB and acidic and basic fibroblast growth factors, all strong activators of fibroblast proliferation, but not by epidermal growth factor and interleukin-4. In a murine hematopoietic progenitor cell line, San5 transcript induction strictly correlated with [(3)H]thymidine uptake. Isolation and sequencing of the murine San5 cDNA revealed amino acid sequence homology to yeast Nop5p, a nucleolar protein required for pre-rRNA processing and ribosome assembly. Strikingly, SAN5 was able to rescue a nop5 null mutant, implicating SAN5 in the process of ribosome biogenesis. Consistent with this result, SAN5 was localized to the nucleolus in both yeast and mouse. Thus, San5 may provide a link between growth factor receptor activation and the cellular translational machinery.
Insights
Researchers identified San5, a novel gene induced by growth factors like PDGF. This gene is crucial for ribosome biogenesis and links growth factor signaling to the cell
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Receptor tyrosine kinases (RTKs) regulate normal and neoplastic growth.
- Identifying RTK-activated genes is key to understanding cellular growth.
- Platelet-derived growth factor (PDGF) is a potent mitogen involved in cell proliferation.
Purpose of the Study:
- To identify novel genes transcriptionally activated by growth factors.
- To elucidate the role of growth factor-induced genes in cellular processes.
Main Methods:
- Differential display reverse transcription-polymerase chain reaction (DD-RT-PCR) was used to identify novel cDNAs.
- San5 cDNA was isolated and sequenced from NIH 3T3 fibroblasts.
- Functional assays were performed in yeast (nop5 null mutant rescue) and murine cells.
Main Results:
- A novel growth factor-induced cDNA, San5, was identified.
- San5 transcript levels increased rapidly in response to PDGF and fibroblast growth factors.
- San5 shares homology with yeast Nop5p and rescues a nop5 null mutant, indicating a role in ribosome biogenesis.
- San5 is localized to the nucleolus in both yeast and mouse cells.
Conclusions:
- San5 is a novel gene induced by mitogenic growth factors.
- San5 plays a critical role in ribosome biogenesis.
- San5 may link growth factor receptor activation to the cellular translational machinery.