IMPACT is a GCN2 inhibitor that limits lifespan in Caenorhabditis elegans

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dc.citation.volume14
dc.contributor.authorFerraz, Rafael C. [UNIFESP]
dc.contributor.authorCamara, Henrique [UNIFESP]
dc.contributor.authorSouza, Evandro Araujo de [UNIFESP]
dc.contributor.authorPinto, Silas [UNIFESP]
dc.contributor.authorPinca, Ana Paula Forti [UNIFESP]
dc.contributor.authorSilva, Richard Cardoso da [UNIFESP]
dc.contributor.authorSato, Vitor Neves [UNIFESP]
dc.contributor.authorCastilho, Beatriz Amaral de [UNIFESP]
dc.contributor.authorMori, Marcelo Alves da Silva [UNIFESP]
dc.coverageLondon
dc.date.accessioned2020-07-31T12:47:34Z
dc.date.available2020-07-31T12:47:34Z
dc.date.issued2016
dc.description.abstractBackground: The General Control Nonderepressible 2 (GCN2) kinase is a conserved member of the integrated stress response (ISR) pathway that represses protein translation and helps cells to adapt to conditions of nutrient shortage. As such, GCN2 is required for longevity and stress resistance induced by dietary restriction (DR). IMPACT is an ancient protein that inhibits GCN2. Results: Here, we tested whether IMPACT down-regulation mimics the effects of DR in C. elegans. Knockdown of the C. elegans IMPACT homolog impt-1 activated the ISR pathway and increased lifespan and stress resistance of worms in a gcn-2-dependent manner. Impt-1 knockdown exacerbated DR-induced longevity and required several DR-activated transcription factors to extend lifespan, among them SKN-1 and DAF-16, which were induced during larval development and adulthood, respectively, in response to impt-1 RNAi. Conclusions: IMPACT inhibits the ISR pathway, thus limiting the activation of stress response factors that are beneficial during aging and required under DR.en
dc.description.affiliationUniv Fed Sao Paulo, Escola Paulista Med, Dept Biophys, Sao Paulo, Brazil
dc.description.affiliationUniv Estadual Campinas, Dept Biochem & Tissue Biol, Campinas, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Sao Paulo, Brazil
dc.description.affiliationUnifespDepartment of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
dc.description.affiliationUnifespDepartment of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipNational Institutes of Health (NIH) Office of Research Infrastructure Programs
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIDNIH Office of Research Infrastructure Programs: P40 OD010440
dc.description.sponsorshipIDCNPq: 444424/2014-8
dc.description.sponsorshipIDCNPq: 474397/2011-4
dc.description.sponsorshipIDFAPESP: 2010/52557-0
dc.description.sponsorshipIDFAPESP: 2015/01316-7
dc.description.sponsorshipIDFAPESP: 2015/04264-8
dc.description.sponsorshipIDFAPESP: 2012/24490-4
dc.description.sponsorshipIDFAPESP: 2009/52047-5
dc.description.sponsorshipIDFAPESP: 2014/17145-4
dc.description.sponsorshipIDFAPESP: 2012/04064-0
dc.description.sponsorshipIDFAPESP: 2014/25068-0
dc.description.sponsorshipIDFAPESP: 2014/25270-3
dc.description.sponsorshipIDFAPESP: 2014/10814-8
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1186/s12915-016-0301-2
dc.identifier.citationBmc Biology. London, v. 14, p. -, 2016.
dc.identifier.doi10.1186/s12915-016-0301-2
dc.identifier.fileWOS000384947100001.pdf
dc.identifier.issn1741-7007
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/56908
dc.identifier.wosWOS:000384947100001
dc.language.isoeng
dc.publisherBiomed Central Ltd
dc.relation.ispartofBmc Biology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectIMPACTen
dc.subjectGCN2en
dc.subjectDietary restrictionen
dc.subjectIntegrated stress responseen
dc.subjectAgingen
dc.titleIMPACT is a GCN2 inhibitor that limits lifespan in Caenorhabditis elegansen
dc.typeinfo:eu-repo/semantics/article
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