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A more recent version of this article appeared on March 5, 2004
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Papers In Press, published online ahead of print December 19, 2003
J. Biol. Chem, 10.1074/jbc.M307735200
Submitted on July 17, 2003
Revised on December 17, 2003
Accepted on December 19, 2003

Phosphatidylinositol-3 kinase and mTOR signaling pathways regulate RNA Polymerase I transcription in response to IGF-1 and nutrients

Martyn J. James and Joost C.B.M. Zomerdijk

Division of Gene Regulation and Expression, Wellcome Trust Biocentre, Faculty of Life Sciences, Dundee DD1 5EK

Corresponding Author: j.zomerdijk{at}dundee.ac.uk

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-induced Pol I transcription in HEK293 cells is entirely dependent on Phosphatidylinositol-3 Kinase activity and, additionally, is modulated by the mammalian Target Of Rapamycin, which coordinates Pol I transcription with the availability of amino acids. The Mitogen Activated Protein Kinase 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.


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