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Anti-diabetic and anti-obesity agent sodium tungstate enhances GCN pathway activation through Glc7p inhibition

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Anti-diabetic and anti-obesity agent sodium tungstate enhances GCN pathway activation through Glc7p inhibition

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dc.contributor.author Rodríguez Hernández, Carlos Javier es_ES
dc.contributor.author Guinovart, J.J. es_ES
dc.contributor.author Murguía, Jose R. es_ES
dc.date.accessioned 2017-03-06T11:34:10Z
dc.date.available 2017-03-06T11:34:10Z
dc.date.issued 2012-02-03
dc.identifier.issn 0014-5793
dc.identifier.uri http://hdl.handle.net/10251/78514
dc.description.abstract [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. es_ES
dc.description.sponsorship 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).
dc.language Inglés es_ES
dc.publisher Elsevier es_ES
dc.publisher Wiley es_ES
dc.relation DGICYT/BFU2008-00769 es_ES
dc.relation GC/2009 SGR 01176 es_ES
dc.relation FIS/FIS03-0628 es_ES
dc.relation.ispartof FEBS Letters es_ES
dc.rights Reconocimiento - No comercial - Sin obra derivada (by-nc-nd) es_ES
dc.subject Tungstate es_ES
dc.subject Translational control es_ES
dc.subject Phosphatase es_ES
dc.subject Diabetes es_ES
dc.subject Nutrient stress es_ES
dc.subject.classification BIOQUIMICA Y BIOLOGIA MOLECULAR es_ES
dc.title Anti-diabetic and anti-obesity agent sodium tungstate enhances GCN pathway activation through Glc7p inhibition es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1016/j.febslet.2011.12.035
dc.rights.accessRights Abierto es_ES
dc.contributor.affiliation 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 es_ES
dc.contributor.affiliation Universitat Politècnica de València. Escuela Técnica Superior de Ingeniería Agronómica y del Medio Natural - Escola Tècnica Superior d'Enginyeria Agronòmica i del Medi Natural es_ES
dc.description.bibliographicCitation 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. doi:10.1016/j.febslet.2011.12.035 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion http://onlinelibrary.wiley.com/doi/10.1016/j.febslet.2011.12.035/full es_ES
dc.description.upvformatpinicio 270 es_ES
dc.description.upvformatpfin 276 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 586 es_ES
dc.description.issue 3 es_ES
dc.relation.senia 232608 es_ES
dc.identifier.eissn 1873-3468
dc.identifier.pmid 22245679
dc.contributor.funder Dirección General de Investigación Científica y Técnica
dc.contributor.funder Generalitat de Catalunya
dc.contributor.funder Fondo de Investigaciones Sanitarias


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