| Texto completo | |
| Autor(es): |
Silva, Richard C.
;
Sattlegger, Evelyn
;
Castilho, Beatriz A.
Número total de Autores: 3
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Journal of Cell Science; v. 129, n. 24, p. 4521-4533, DEC 15 2016. |
| Citações Web of Science: | 8 |
| Resumo | |
Genetic and pharmacological interventions in yeast and mammalian cells have suggested a cross-talk between the actin cytoskeleton and protein synthesis. Regulation of the activity of the translation initiation factor 2 (eIF2) is a paramount mechanism for cells to rapidly adjust the rate of protein synthesis and to trigger reprogramming of gene expression in response to internal and external cues. Here, we show that disruption of F-actin in mammalian cells inhibits translation in a GCN2-dependent manner, correlating with increased levels of uncharged tRNA. GCN2 activation increased phosphorylation of its substrate eIF2a and the induction of the integrated stress response master regulator, ATF4. GCN2 activation by latrunculin-B is dependent on GCN1 and inhibited by IMPACT. Our data suggest that GCN2 occurs in two different complexes, GCN2-eEF1A and GCN2-GCN1. Depolymerization of F-actin shifts GCN2 to favor the complex with GCN1, concomitant with GCN1 being released from its binding to IMPACT, which is sequestered by G-actin. These events might further contribute to GCN2 activation. Our findings indicate that GCN2 is an important sensor of the state of the actin cytoskeleton. (AU) | |
| Processo FAPESP: | 14/17145-4 - Regulação traducional mediada por GCN2: modulação pelo citoesqueleto de actina |
| Beneficiário: | Richard Cardoso da Silva |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 14/23889-6 - GCN1 e seu ligante Yih1/IMPACT: funções no controle traducional e outras |
| Beneficiário: | Beatriz Amaral de Castilho |
| Modalidade de apoio: | Auxílio à Pesquisa - Pesquisador Visitante - Internacional |
| Processo FAPESP: | 09/52047-5 - Regulação traducional mediada por EIF2 em eucariotos |
| Beneficiário: | Beatriz Amaral de Castilho |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |