PMID- 14688273 OWN - NLM STAT- MEDLINE DCOM- 20040706 LR - 20211203 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 279 IP - 10 DP - 2004 Mar 5 TI - Phosphatidylinositol 3-kinase and mTOR signaling pathways regulate RNA polymerase I transcription in response to IGF-1 and nutrients. PG - 8911-8 AB - Regulation of ribosomal RNA gene transcription by RNA polymerase I (Pol I) is fundamental to ribosome biogenesis and therefore protein translation capacity and cell growth, yet little is known of the key signaling cascades involved. We show here that insulin-like growth factor-1 (IGF-1)-induced Pol I transcription in HEK293 cells is entirely dependent on phosphatidylinositol 3-kinase (PI3K) activity and, additionally, is modulated by the mammalian target of rapamycin (mTOR), which coordinates Pol I transcription with the availability of amino acids. The mitogen-activated protein kinase (MAPK) pathway is weakly stimulated by IGF-1 in these cells and partly contributes to Pol I transcription regulation. Activation of Pol I transcription by IGF-1 results from enhancement of the activity of the Pol I transcription machinery and increased occupancy by SL1 of the endogenous tandemly repeated ribosomal promoters in vivo. The inputs from PI3K, mTOR, and MAPK pathways converge to direct appropriate rRNA gene expression by Pol I in the nucleolus of mammalian cells in response to environmental cues, such as growth factors and nutrients. FAU - James, Martyn J AU - James MJ AD - Division of Gene Regulation and Expression, Wellcome Trust Biocentre, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom. FAU - Zomerdijk, Joost C B M AU - Zomerdijk JC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20031219 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (RNA, Spliced Leader) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.7.6 (RNA Polymerase I) SB - IM EIN - J Biol Chem. 2020 May 15;295(20):7178. PMID: 32414913 MH - Cell Line MH - Gene Expression Regulation/drug effects MH - Humans MH - Insulin-Like Growth Factor I/*pharmacology MH - MAP Kinase Signaling System MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Promoter Regions, Genetic MH - Protein Kinases/*metabolism MH - RNA Polymerase I/*biosynthesis/genetics MH - RNA, Spliced Leader MH - Signal Transduction MH - TOR Serine-Threonine Kinases MH - Transcription, Genetic/drug effects EDAT- 2003/12/23 05:00 MHDA- 2004/07/09 05:00 CRDT- 2003/12/23 05:00 PHST- 2003/12/23 05:00 [pubmed] PHST- 2004/07/09 05:00 [medline] PHST- 2003/12/23 05:00 [entrez] AID - S0021-9258(17)47795-7 [pii] AID - 10.1074/jbc.M307735200 [doi] PST - ppublish SO - J Biol Chem. 2004 Mar 5;279(10):8911-8. doi: 10.1074/jbc.M307735200. Epub 2003 Dec 19.