IMPACT is a GCN2 inhibitor that limits lifespan in Caenorhabditis elegans

Show simple item record

dc.contributor.author Ferraz, Rafael C. [UNIFESP]
dc.contributor.author Camara, Henrique [UNIFESP]
dc.contributor.author Souza, Evandro Araujo de [UNIFESP]
dc.contributor.author Pinto, Silas [UNIFESP]
dc.contributor.author Pinca, Ana Paula Forti [UNIFESP]
dc.contributor.author Silva, Richard Cardoso da [UNIFESP]
dc.contributor.author Sato, Vitor Neves [UNIFESP]
dc.contributor.author Castilho, Beatriz Amaral de [UNIFESP]
dc.contributor.author Mori, Marcelo Alves da Silva [UNIFESP]
dc.date.accessioned 2020-07-31T12:47:34Z
dc.date.available 2020-07-31T12:47:34Z
dc.date.issued 2016
dc.identifier http://dx.doi.org/10.1186/s12915-016-0301-2
dc.identifier.citation Bmc Biology. London, v. 14, p. -, 2016.
dc.identifier.issn 1741-7007
dc.identifier.uri https://repositorio.unifesp.br/handle/11600/56908
dc.description.abstract Background: 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.sponsorship National Institutes of Health (NIH) Office of Research Infrastructure Programs
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.format.extent -
dc.language.iso eng
dc.publisher Biomed Central Ltd
dc.relation.ispartof Bmc Biology
dc.rights Acesso aberto
dc.subject IMPACT en
dc.subject GCN2 en
dc.subject Dietary restriction en
dc.subject Integrated stress response en
dc.subject Aging en
dc.title IMPACT is a GCN2 inhibitor that limits lifespan in Caenorhabditis elegans en
dc.type Artigo
dc.description.affiliation Univ Fed Sao Paulo, Escola Paulista Med, Dept Biophys, Sao Paulo, Brazil
dc.description.affiliation Univ Estadual Campinas, Dept Biochem & Tissue Biol, Campinas, SP, Brazil
dc.description.affiliation Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Sao Paulo, Brazil
dc.description.affiliationUnifesp Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
dc.description.affiliationUnifesp Department of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
dc.description.sponsorshipID NIH Office of Research Infrastructure Programs: P40 OD010440
dc.description.sponsorshipID CNPq: 444424/2014-8
dc.description.sponsorshipID CNPq: 474397/2011-4
dc.description.sponsorshipID FAPESP: 2010/52557-0
dc.description.sponsorshipID FAPESP: 2015/01316-7
dc.description.sponsorshipID FAPESP: 2015/04264-8
dc.description.sponsorshipID FAPESP: 2012/24490-4
dc.description.sponsorshipID FAPESP: 2009/52047-5
dc.description.sponsorshipID FAPESP: 2014/17145-4
dc.description.sponsorshipID FAPESP: 2012/04064-0
dc.description.sponsorshipID FAPESP: 2014/25068-0
dc.description.sponsorshipID FAPESP: 2014/25270-3
dc.description.sponsorshipID FAPESP: 2014/10814-8
dc.identifier.file WOS000384947100001.pdf
dc.identifier.doi 10.1186/s12915-016-0301-2
dc.description.source Web of Science
dc.identifier.wos WOS:000384947100001
dc.coverage London
dc.citation.volume 14



File

Name: WOS000384947100001.pdf
Size: 1.549Mb
Format: PDF
Description:
Open file

This item appears in the following Collection(s)

Show simple item record

Search


Browse

Statistics

My Account