TORC1 and TORC2 work together to regulate ribosomal protein S6 phosphorylation in Saccharomyces cerevisiae
العنوان: | TORC1 and TORC2 work together to regulate ribosomal protein S6 phosphorylation in Saccharomyces cerevisiae |
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المؤلفون: | Pavel V. Baranov, Michael Costanzo, Romika Kumari, Seda Yerlikaya, Charles Boone, Gustav Ammerer, Robbie Loewith, Dorothea Anrather, Madeleine Meusburger, Alexandre Huber |
المصدر: | Molecular Biology of the Cell Molecular Biology of the Cell, Vol. 27, No 2 (2016) pp. 397-409 |
بيانات النشر: | Scientific Society Publisher Alliance, 2015. |
سنة النشر: | 2015 |
مصطلحات موضوعية: | 0301 basic medicine, mTORC1, TOR Serine-Threonine Kinases/metabolism, Small, Saccharomyces cerevisiae/metabolism, ddc:590, Multiprotein Complexes/metabolism, Ribosome Subunits, TOR complex, Ribosome profiling, Phosphorylation, Genetics, Ribosomal Protein S6, Kinase, Phosphorylation/physiology, TOR Serine-Threonine Kinases, Polyribosomes/metabolism, Translation (biology), Protein-Serine-Threonine Kinases/metabolism, Articles, Saccharomyces cerevisiae Proteins/metabolism, Cell biology, Ribosomal protein s6, Ribsomal protein, Signal Transduction, Saccharomyces cerevisiae Proteins, S6, Mechanistic Target of Rapamycin Complex 2, macromolecular substances, Saccharomyces cerevisiae, Biology, Mechanistic Target of Rapamycin Complex 1, Protein Serine-Threonine Kinases, Eukaryotic/metabolism, 03 medical and health sciences, ddc:570, Transcription Factors/metabolism, Ribosomes/metabolism, Kinase activity, Molecular Biology, Ribosome Subunits, Small, Eukaryotic, Cell Biology, Signaling, TORC2, TORC1, Ribosomal Protein S6/genetics/metabolism, 030104 developmental biology, Multiprotein Complexes, Polyribosomes, Signal Transduction/genetics, Ribosomes, Transcription Factors |
الوصف: | Phosphorylation of the S6 protein of the 40S subunit of the eukaryote ribosome downstream of anabolic signals has long been assumed to promote protein synthesis. Both target of rapamycin complexes regulate this modification in yeast, but the use of ribosome profiling shows no role for Rps6 phosphorylation in mRNA translation. Nutrient-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. |
وصف الملف: | application/pdf |
اللغة: | English |
تدمد: | 1059-1524 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fa7eaf3eca1d771f3edc00e0ac747fb8 https://hdl.handle.net/10468/9287 |
Rights: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....fa7eaf3eca1d771f3edc00e0ac747fb8 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 10591524 |
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