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.
Highlights
Investigations have sought to explain the molecular mechanisms by which growth factor binding to receptor elicits functional responses via the induction of specific gene transcripts [1,2,3]
San5 Complements a Lethal Defect in Yeast Ribosome Biogenesis—Since murine SAN5 shares some amino acid sequence homology with yeast Nop5p/Nop58p, we investigated whether San5 might complement yeast containing a disruption of NOP5, which is essential for growth [36, 37]
We exploited differential display reverse transcription technology to isolate a novel murine gene, San5, that was induced by multiple growth factors coincident with cell cycle progression
Summary
13835–13841, 2000 Printed in U.S.A. Multiple Growth Factor Induction of a Murine Early Response Gene That Complements a Lethal Defect in Yeast Ribosome Biogenesis*. 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). Investigations have sought to explain the molecular mechanisms by which growth factor binding to receptor elicits functional responses via the induction of specific gene transcripts [1,2,3]. We exploited differential display reverse transcription technology to isolate a delayed early response gene induced by multiple growth factors that complements a lethal defect in yeast ribosome biogenesis
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