TORC1 and TORC2 work together to regulate ribosomal protein S6 phosphorylation in Saccharomyces cerevisiae

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dc.contributor.authorYerlikaya, Seda
dc.contributor.authorMeusburger, Madeleine
dc.contributor.authorKumari, Romika
dc.contributor.authorHuber, Alexandre
dc.contributor.authorAnrather, Dorothea
dc.contributor.authorCostanzo, Michael
dc.contributor.authorBoone, Charles
dc.contributor.authorAmmerer, Gustav
dc.contributor.authorBaranov, Pavel V.
dc.contributor.authorLoewith, Robbie
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderEuropean Research Councilen
dc.contributor.funderSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschungen
dc.contributor.funderCanton de Genèveen
dc.date.accessioned2019-12-03T09:19:53Z
dc.date.available2019-12-03T09:19:53Z
dc.date.issued2015-11-18
dc.description.abstractNutrient-sensitive phosphorylation of the S6 protein of the 40S subunit of the eukaryote ribosome is highly conserved. However, despite four decades of research, the functional consequences of this modification remain unknown. Revisiting this enigma in Saccharomyces cerevisiae, we found that the regulation of Rps6 phosphorylation on Ser-232 and Ser-233 is mediated by both TOR complex 1 (TORC1) and TORC2. TORC1 regulates phosphorylation of both sites via the poorly characterized AGC-family kinase Ypk3 and the PP1 phosphatase Glc7, whereas TORC2 regulates phosphorylation of only the N-terminal phosphosite via Ypk1. Cells expressing a nonphosphorylatable variant of Rps6 display a reduced growth rate and a 40S biogenesis defect, but these phenotypes are not observed in cells in which Rps6 kinase activity is compromised. Furthermore, using polysome profiling and ribosome profiling, we failed to uncover a role of Rps6 phosphorylation in either global translation or translation of individual mRNAs. Taking the results together, this work depicts the signaling cascades orchestrating Rps6 phosphorylation in budding yeast, challenges the notion that Rps6 phosphorylation plays a role in translation, and demonstrates that observations made with Rps6 knock-ins must be interpreted cautiously.en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationYerlikaya, S., Meusburger, M., Kumari, R., Huber, A., Anrather, D., Costanzo, M., Boone, C., Ammerer, G., Baranov, P. V. and Loewith, R. (2016) 'TORC1 and TORC2 work together to regulate ribosomal protein S6 phosphorylation in Saccharomyces cerevisiae', Molecular Biology of the Cell, 27(2), pp. 397-409. doi: 10.1091/mbc.E15-08-0594en
dc.identifier.doi10.1091/mbc.E15-08-0594en
dc.identifier.eissn1939-4586
dc.identifier.issn1059-1524
dc.identifier.issued2en
dc.identifier.journaltitleMolecular Biology of the Cellen
dc.identifier.startpage397en
dc.identifier.urihttps://hdl.handle.net/10468/9287
dc.identifier.volume27en
dc.language.isoenen
dc.publisherScientific Society Publisher Allianceen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Investigator Programme/12/IA/1335/IE/Development of computational resources for the analysis of Genome Wide Information on Protein Synthesis (GWIPS)./en
dc.rights© 2016 Yerlikaya, Meusburger, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0en
dc.subjectTORC1en
dc.subjectTORC2en
dc.subjectRibsomal proteinen
dc.subjectS6en
dc.subjectPhosphorylationen
dc.subjectSaccharomyces cerevisiaeen
dc.titleTORC1 and TORC2 work together to regulate ribosomal protein S6 phosphorylation in Saccharomyces cerevisiaeen
dc.typeArticle (peer-reviewed)en
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