RRC ID |
54951
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著者 |
Sriskanthadevan-Pirahas S, Lee J, Grewal SS.
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タイトル |
The EGF/Ras pathway controls growth in Drosophila via ribosomal RNA synthesis.
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ジャーナル |
Dev Biol
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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.
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巻・号 |
439(1)
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ページ |
19-29
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公開日 |
2018-7-1
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DOI |
10.1016/j.ydbio.2018.04.006
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PII |
S0012-1606(17)30823-0
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PMID |
29660312
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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
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引用数 |
7
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リソース情報 |
ショウジョウバエ |
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