RRC ID 54951
著者 Sriskanthadevan-Pirahas S, Lee J, Grewal SS.
タイトル The EGF/Ras pathway controls growth in Drosophila via ribosomal RNA synthesis.
ジャーナル Dev Biol
Abstract The Ras small G-protein is a conserved regulator of cell and tissue growth during animal development. Studies in Drosophila have shown how Ras can stimulate a RAF-MEK-ERK signalling pathway to control cell growth and proliferation in response to Epidermal Growth Factor (EGF) stimulation. This work has also defined several transcription factors that can function as downstream growth effectors of the EGF/Ras/ERK pathway by stimulating mRNA transcription. Here we report on stimulation of RNA polymerase I (Pol I)-mediated ribosomal RNA (rRNA) synthesis as a growth effector of Ras/ERK signalling in Drosophila. We show that Ras/ERK signalling promotes an increase in nucleolar size in larval wing discs, which is indicative of increased ribosome synthesis. We also find that activation of Ras/ERK signalling promotes rRNA synthesis both in vivo and in cultured Drosophila S2 cells. We show that Ras signalling can regulate the expression of the Pol I transcription factor TIF-IA, and that this regulation requires dMyc. Finally, we find that TIF-IA-mediated rRNA synthesis is required for Ras/ERK signalling to drive proliferation in both larval and adult Drosophila tissues. These findings indicate that Ras signalling can promote ribosome synthesis in Drosophila, and that this is one mechanism that contributes to the growth effects of the Ras signalling pathway.
巻・号 439(1)
ページ 19-29
公開日 2018-7-1
DOI 10.1016/j.ydbio.2018.04.006
PII S0012-1606(17)30823-0
PMID 29660312
MeSH Animals Cell Proliferation Drosophila / genetics Drosophila / metabolism Drosophila Proteins / genetics Drosophila Proteins / metabolism Drosophila Proteins / physiology* Epidermal Growth Factor / metabolism Epidermal Growth Factor / physiology* Gene Expression Regulation / physiology IMP Dehydrogenase / metabolism IMP Dehydrogenase / physiology* Larva / metabolism RNA, Ribosomal / biosynthesis* RNA, Ribosomal / metabolism RNA, Ribosomal / physiology Ribosomes / metabolism Signal Transduction Transcription Factors / metabolism Transcription, Genetic / physiology
IF 2.936
引用数 7
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