Rodríguez Hernández, CJ.; Guinovart, J.; Murguía, JR. (2012). Anti-diabetic and anti-obesity agent sodium tungstate enhances GCN pathway activation through Glc7p inhibition. FEBS Letters. 586(3):270-276. https://doi.org/10.1016/j.febslet.2011.12.035
Por favor, use este identificador para citar o enlazar este ítem: http://hdl.handle.net/10251/78514
Title:
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Anti-diabetic and anti-obesity agent sodium tungstate enhances GCN pathway activation through Glc7p inhibition
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Author:
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Rodríguez Hernández, Carlos Javier
Guinovart, J.J.
Murguía, Jose R.
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UPV Unit:
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Universitat Politècnica de València. Instituto Universitario Mixto de Biología Molecular y Celular de Plantas - Institut Universitari Mixt de Biologia Molecular i Cel·lular de Plantes
Universitat Politècnica de València. Escuela Técnica Superior de Ingeniería Agronómica y del Medio Natural - Escola Tècnica Superior d'Enginyeria Agronòmica i del Medi Natural
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Issued date:
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Abstract:
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[EN] Tungstate counteracts diabetes and obesity in animal models, but its molecular mechanisms remain elusive. Our Saccharomyces cerevisiae-based approach has found that tungstate alleviated the growth defect induced by ...[+]
[EN] Tungstate counteracts diabetes and obesity in animal models, but its molecular mechanisms remain elusive. Our Saccharomyces cerevisiae-based approach has found that tungstate alleviated the growth defect induced by nutrient stress and enhanced the activation of the GCN pathway. Tungstate relieved the sensitivity to starvation of a gcn2-507 yeast hypomorphic mutant, indicating that tungstate modulated the GCN pathway downstream of Gcn2p. Interestingly, tungstate inhibited Glc7p and PP1 phosphatase activity, both negative regulators of the GCN pathway in yeast and humans, respectively. Accordingly, overexpression of a dominant-negative Glc7p mutant in yeast mimicked tungstate effects. Therefore tungstate alleviates nutrient stress in yeast by in vivo inhibition of Glc7p. These data uncover a potential role for tungstate in the treatment of PP1 and GCN related diseases. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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Subjects:
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Tungstate
,
Translational control
,
Phosphatase
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Diabetes
,
Nutrient stress
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Copyrigths:
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Reconocimiento - No comercial - Sin obra derivada (by-nc-nd)
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Source:
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FEBS Letters. (issn:
0014-5793
) (eissn:
1873-3468
)
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DOI:
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10.1016/j.febslet.2011.12.035
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Publisher:
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Elsevier
Wiley
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Publisher version:
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http://onlinelibrary.wiley.com/doi/10.1016/j.febslet.2011.12.035/full
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Project ID:
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info:eu-repo/grantAgreement/MICINN//BFU2008-00769/ES/ESTUDIO DE UN NUEVO MECANISMO DE REGULACION DEL METABOLISMO DEL GLUCOGENO. ANALISIS DE LAS IMPLICACIONES PATOLOGICAS DE LA ACUMULACION ANOMALA DE POLIMEROS DE GLUCOSA/
info:eu-repo/grantAgreement/Generalitat de Catalunya//2009 SGR 01176/
info:eu-repo/grantAgreement/ISCIII//FIS03-0628/
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Thanks:
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We thank R. Serrano for providing the Delta cnb1 mutant strain. We thank A. G. Hinnebusch for the gcn2-507 and gcn2 mutant strains. The pGEX-GLC7 plasmid was kindly provided by P. Sanz. The PP1-FLAG construct was kindly ...[+]
We thank R. Serrano for providing the Delta cnb1 mutant strain. We thank A. G. Hinnebusch for the gcn2-507 and gcn2 mutant strains. The pGEX-GLC7 plasmid was kindly provided by P. Sanz. The PP1-FLAG construct was kindly provided by A. C. Gingras. We thank T. Yates and J. Calbo for critical reading of the manuscript and helpful suggestions. J. J. Guinovart's laboratory was funded by grants from the Direccion General de Investigacion Cientifica y Tecnica (BFU2008-00769), the Generalitat de Catalunya (2009 SGR 01176), the Fundacion Marcelino Botin and the CIBER de Diabetes y Enfermedades Metabolicas Asociadas (ISCIII, Ministerio de Ciencia e Innovacion). J. R. Murguia laboratory was funded by Fondo de Investigaciones Sanitarias (FIS03-0628).
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Type:
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Artículo
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