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

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.

Increased Expression of a Nucleolar Nop5/Sik Family Member in Metastatic Melanoma Cells

“…The sequence is the most probable mouse counterpart for yeast Nop58 (yNop58), because there is 47% identity and 71% similarity between mNop58 and yNop58. On the other hand, Nelson and colleagues 44 isolated a novel mouse member of the Nop58 subgroup from a NIH3T3 cDNA library, and termed it SAN5. In the present study, we isolated clones encoding Sik-SP from a BL6 cDNA library.…”

“…Recently, SAN5, another mouse member of the Nop5/Sik family, was shown to locate to the nucleolus. 44 To learn the subcellular localization of Sik-SP, COS-7 cells were transfected with a plasmid encoding the GFP-tagged form of Sik-SP. Because an abundance of lysine residues in the C-terminal region is characteristic of the Nop5/Sik family members, [23][24][25]29,30 we wished to know whether the C-terminal region is important for the localization of Sik-SP.…”

Fibroblast Growth Factor 2 Is Necessary for the Growth of Glutamate Projection Neurons in the Anterior Neocortex

“…Ras and its downstream effector Myc, as well as S6 kinases, also regulate cell hypertrophy by inducing protein synthesis, translation initiation factors, and nucleolar structural proteins (Dang, 1999;Kim et al, 2000;Edgar, 2000, 2001). Fgf2 has been shown to induce an early response gene involved in ribosomal protein synthesis, and it is required for the hypertrophy of cardiac myocites in response to a pressure load (Nelson et al, 2000).…”

Proteomic snapshot analyses of preribosomal ribonucleoprotein complexes formed at various stages of ribosome biogenesis in yeast and mammalian cells

“…However, in the isolated mammalian pre-rRNP complexes, we have also identified a number of nonribosomal proteins, which do not have a counterpart in the yeast pre-rRNP complexes. Those proteins could function uniquely in the process of mammalian ribosome biogenesis and/or its related processes of mammalian cells, and might be downstream targets of some of the oncogenes and growth-factor receptors, which are shown to be major regulators of the protein-synthesis machinery (Nelson et al, 2000;Boon et al, 2001;Kroll, Barth-Baus, & Hensold, 2001). We suspect that regulatory mechanisms that underlie ribosome biogenesis of mammalian cells are much more diversified than those of yeast cells because adaptation, growth, and proliferation of distinctly different cell types, each of which is dependent on different growth factors and other stimuli, are directly coupled with the regulatory mechanisms of ribosome biogenesis in mammalian cells.…”

“…In addition, downstream targets of oncogenes (such as Nmyc), as well as of growth-factor receptors (such as those for platelet growth factors, fibroblast growth factors, etc.) are shown to be major regulators of the protein synthesis machinery (Nelson et al, 2000;Boon et al, 2001;Kroll, Barth-Baus, & Hensold, 2001). Thus, that focus renewed attention on the regulatory mechanism that underlies ribosome biogenesis.…”