p38 MAPK controls prothrombin expression by regulated RNA 3' end processing.
Mol Cell
; 41(3): 298-310, 2011 Feb 04.
Article
em En
| MEDLINE
| ID: mdl-21292162
ABSTRACT
Thrombin is a key protease involved in blood coagulation, complement activation, inflammation, angiogenesis, and tumor invasion. Although induced in many (patho-)physiological conditions, the underlying mechanisms controlling prothrombin expression remained enigmatic. We have now discovered that prothrombin expression is regulated by a posttranscriptional regulatory mechanism responding to stress and inflammation. This mechanism is triggered by external stimuli that activate p38 MAPK. In turn, p38 MAPK upmodulates canonical 3' end processing components and phosphorylates the RNA-binding proteins FBP2 and FBP3, which inhibit 3' end processing of mRNAs, such as prothrombin mRNA, that bear a defined upstream sequence element (USE) in their 3'UTRs. Upon phosphorylation, FBP2 and FBP3 dissociate from the USE, making it accessible to proteins that stimulate 3' end processing. We provide in vivo evidence suggesting the importance of this mechanism in inflammatory hypercoagulation and tumor invasion. Regulated 3' end processing thus emerges as a key mechanism of gene regulation with broad biological and medical implications.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Protrombina
/
Regulação Enzimológica da Expressão Gênica
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Processamento de Terminações 3' de RNA
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Proteínas Quinases p38 Ativadas por Mitógeno
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article