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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

IMPACT is a GCN2 inhibitor that limits lifespan in Caenorhabditis elegans

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Author(s):
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.
Total Authors: 9
Document type: Journal article
Source: BMC Biology; v. 14, OCT 7 2016.
Web of Science Citations: 6
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. (AU)

FAPESP's process: 09/52047-5 - Translational regulation mediated by elF2 in eukaryotes
Grantee:Beatriz Amaral de Castilho
Support type: Research Projects - Thematic Grants
FAPESP's process: 14/10814-8 - Determination of factors that controls Dicer expression in vivo in C. elegans
Grantee:Evandro Araújo de Souza
Support type: Scholarships in Brazil - Master
FAPESP's process: 15/04264-8 - Phenotypic screen of nematodes C. elegans mutants for proteins necessary to systemic RNAi
Grantee:Henrique Camara
Support type: Scholarships in Brazil - Master
FAPESP's process: 14/25068-0 - Unraveling new mechanisms responsible for the cell non-autonomous control of proteostasis in c. elegans
Grantee:Ana Paula Forti Pinca
Support type: Scholarships in Brazil - Master
FAPESP's process: 15/01316-7 - Dicer, miRNAs and the control of mitochondrial function in the context of aging and caloric restriction
Grantee:Marcelo Alves da Silva Mori
Support type: Regular Research Grants
FAPESP's process: 14/25270-3 - Study of Dicer effects on mitochondrial function, metabolism and aging in nematodes C. elegans
Grantee:Silas Pinto da Silva
Support type: Scholarships in Brazil - Master
FAPESP's process: 12/24490-4 - Study of the involvement of impact in the effects of caloric restriction in c. elegans
Grantee:Rafael Ferraz Bannitz
Support type: Scholarships in Brazil - Master
FAPESP's process: 14/17145-4 - Translational regulation mediated by GCN2: modulation by the actin cytoskeleton
Grantee:Richard Cardoso da Silva
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 12/04064-0 - Search for a pharmacological intervention to mimic the beneficial effects of caloric restriction in c. elegans
Grantee:Vitor Neves Sato
Support type: Scholarships in Brazil - Scientific Initiation