MK2-induced tristetraprolin:14-3-3 complexes prevent stress granule association and ARE-mRNA decay.
EMBO J
; 23(6): 1313-24, 2004 Mar 24.
Article
em En
| MEDLINE
| ID: mdl-15014438
ABSTRACT
Stress granules (SGs) are dynamic cytoplasmic foci at which stalled translation initiation complexes accumulate in cells subjected to environmental stress. SG-associated proteins such as TIA-1, TIAR and HuR bind to AU-rich element (ARE)-containing mRNAs and control their translation and stability. Here we show that tristetraprolin (TTP), an ARE-binding protein that destabilizes ARE-mRNAs, is recruited to SGs that are assembled in response to FCCP-induced energy deprivation, but not arsenite-induced oxidative stress. Exclusion of TTP from arsenite-induced SGs is a consequence of MAPKAP kinase-2 (MK2)-induced phosphorylation at serines 52 and 178, which promotes the assembly of TTP14-3-3 complexes. 14-3-3 binding excludes TTP from SGs and inhibits TTP-dependent degradation of ARE-containing transcripts. In activated RAW 264.7 macrophages, endogenous TTP14-3-3 complexes bind to ARE-RNA. Our data reveal the mechanism by which the p38-MAPK/MK2 kinase cascade inhibits TTP-mediated degradation of ARE-containing transcripts and thereby contributes to lipopolysaccharide-induced TNFalpha expression.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
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Proteínas Serina-Treonina Quinases
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Proteínas Imediatamente Precoces
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Estabilidade de RNA
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Sequências Reguladoras de Ácido Ribonucleico
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Proteínas 14-3-3
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Proteínas de Ligação a DNA
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article