Whi2 is a conserved negative regulator of TORC1 in response to low amino acids
| العنوان: | Whi2 is a conserved negative regulator of TORC1 in response to low amino acids |
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| المؤلفون: | Ge He, Nicola L. Diny, Abdel Aouacheria, Margaret Dayhoff-Brannigan, Xianghui Chen, Cierra N. Sing, Zachary D. Stolp, Wen Chih Cheng, Mingjun Zhao, Kyle Metz, J. Marie Hardwick, Xinchen Teng, Guiqin Wang, Yu Zhang |
| المساهمون: | Extraction de Caractéristiques et Identification (imagine), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Beijing National Laboratory for Condensed Matter Physics, Chinese Academy of Sciences [Beijing] (CAS), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Department of Pharmacology and Molecular Sciences, Johns Hopkins University (JHU), National Natural Science Foundation of China 31401197, Natural Science Foundation of Jiangsu Province BK20140318, Jiangsu Key Laboratory of Neuropsychiatric Diseases BM2013003, National Institutes of Health USA [grant numbers R01NS083373 and R01GM077875, Fondation ARC N˚ LS172351, Ligue Contre le Cancer Comité du Gard N˚ LS 176487, Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Université Lumière - Lyon 2 (UL2), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE) |
| المصدر: | PLoS Genetics, Vol 14, Iss 8, p e1007592 (2018) PLoS Genetics PLoS Genetics, 2018, 14 (8), pp.e1007592. ⟨10.1371/journal.pgen.1007592⟩ PLoS Genetics, Public Library of Science, 2018, 14 (8), pp.e1007592. ⟨10.1371/journal.pgen.1007592⟩ |
| بيانات النشر: | Public Library of Science (PLoS), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], GTPase, MESH: Intracellular Signaling Peptides and Proteins/genetics, Chlorocebus aethiops, Phosphoprotein Phosphatases, Amino Acids, [INFO.INFO-BT]Computer Science [cs]/Biotechnology, Genetics (clinical), chemistry.chemical_classification, MESH: Transcription Factors/metabolism, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Intracellular Signaling Peptides and Proteins, MESH: Gene Expression Regulation, Cell biology, Amino acid, MESH: COS Cells, COS Cells, Saccharomyces cerevisiae Proteins, lcsh:QH426-470, Saccharomyces cerevisiae, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Membrane Proteins/genetics, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Skp1, Genetics, Animals, Humans, MESH: Membrane Proteins/metabolism, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], MESH: Transcription Factors/genetics, Molecular Biology, Transcription factor, Ecology, Evolution, Behavior and Systematics, Monomeric GTP-Binding Proteins, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, Membrane Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, biology.organism_classification, MESH: Cercopithecus aethiops, Yeast, lcsh:Genetics, 030104 developmental biology, Gene Expression Regulation, Membrane protein, chemistry, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Transcription Factors, MESH: Intracellular Signaling Peptides and Proteins/metabolism, Genetic screen |
| الوصف: | International audience; Yeast WHI2 was originally identified in a genetic screen for regulators of cell cycle arrest and later suggested to function in general stress responses. However, the function of Whi2 is unknown. Whi2 has predicted structure and sequence similarity to human KCTD family proteins, which have been implicated in several cancers and are causally associated with neurological disorders but are largely uncharacterized. The identification of conserved functions between these yeast and human proteins may provide insight into disease mechanisms. We report that yeast WHI2 is a new negative regulator of TORC1 required to suppress TORC1 activity and cell growth specifically in response to low amino acids. In contrast to current opinion, WHI2 is dispensable for TORC1 inhibition in low glucose. The only widely conserved mechanism that actively suppresses both yeast and mammalian TORC1 specifically in response to low amino acids is the conserved SEACIT/GATOR1 complex that inactivates the TORC1-activating RAG-like GTPases. Unexpectedly, Whi2 acts independently and simultaneously with these established GATOR1-like Npr2-Npr3-Iml1 and RAG-like Gtr1-Gtr2 complexes, and also acts independently of the PKA pathway. Instead, Whi2 inhibits TORC1 activity through its binding partners, protein phosphatases Psr1 and Psr2, which were previously thought to only regulate amino acid levels downstream of TORC1. Furthermore, the ability to suppress TORC1 is conserved in the SKP1/BTB/POZ domain-containing, Whi2-like human protein KCTD11 but not other KCTD family members tested. |
| تدمد: | 1553-7404 1553-7390 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c583efb63eb90e35e76b8524666ee49cTest https://doi.org/10.1371/journal.pgen.1007592Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c583efb63eb90e35e76b8524666ee49c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537404 15537390 |
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