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J Biol Chem, Vol. 275, Issue 18, 13835-13841, May 5, 2000

Multiple Growth Factor Induction of a Murine Early Response Gene That Complements a Lethal Defect in Yeast Ribosome Biogenesis^*

Stefanie A. Nelson, John P. Aris^§, Bharvin K. R. Patel, and William J. LaRochelle^¶

From the  Laboratory of Cellular and Molecular Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892 and the ^§ Department of Anatomy and Cell Biology, Health Science Center, University of Florida College of Medicine, Gainesville, Florida 32610-0235

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 G₁. 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 [³H]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.

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