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IMPACT is a GCN2 inhibitor that limits lifespan in Caenorhabditis elegans.
Ferraz, Rafael C; Camara, Henrique; De-Souza, Evandro A; Pinto, Silas; Pinca, Ana Paula F; Silva, Richard C; Sato, Vitor N; Castilho, Beatriz A; Mori, Marcelo A.
Afiliação
  • Ferraz RC; Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
  • Camara H; Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
  • De-Souza EA; Department of Biochemistry and Tissue Biology, Universidade Estadual de Campinas, Campinas, Brazil.
  • Pinto S; Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
  • Pinca AP; Department of Biochemistry and Tissue Biology, Universidade Estadual de Campinas, Campinas, Brazil.
  • Silva RC; Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
  • Sato VN; Department of Biochemistry and Tissue Biology, Universidade Estadual de Campinas, Campinas, Brazil.
  • Castilho BA; Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
  • Mori MA; Department of Biochemistry and Tissue Biology, Universidade Estadual de Campinas, Campinas, Brazil.
BMC Biol ; 14(1): 87, 2016 10 07.
Article em En | MEDLINE | ID: mdl-27717342
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Quinases / Caenorhabditis elegans / Proteínas de Caenorhabditis elegans / Inibidores de Proteínas Quinases Limite: Animals Idioma: En Revista: BMC Biol Assunto da revista: BIOLOGIA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
Texto completo
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PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Quinases / Caenorhabditis elegans / Proteínas de Caenorhabditis elegans / Inibidores de Proteínas Quinases Limite: Animals Idioma: En Revista: BMC Biol Assunto da revista: BIOLOGIA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido