The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease.
Nat Immunol
; 12(11): 1063-70, 2011 Oct 09.
Article
em En
| MEDLINE
| ID: mdl-21983832
ABSTRACT
Leucine-rich repeat kinase 2 (LRRK2) has been identified by genome-wide association studies as being encoded by a major susceptibility gene for Crohn's disease. Here we found that LRRK2 deficiency conferred enhanced susceptibility to experimental colitis in mice. Mechanistic studies showed that LRRK2 was a potent negative regulator of the transcription factor NFAT and was a component of a complex that included the large noncoding RNA NRON (an NFAT repressor). Furthermore, the risk-associated allele encoding LRRK2 Met2397 identified by a genome-wide association study for Crohn's disease resulted in less LRRK2 protein post-translationally. Severe colitis in LRRK2-deficient mice was associated with enhanced nuclear localization of NFAT1. Thus, our study defines a new step in the control of NFAT activation that involves an immunoregulatory function of LRRK2 and has important implications for inflammatory bowel disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Núcleo Celular
/
Proteínas Serina-Treonina Quinases
/
Colite
/
RNA não Traduzido
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Fatores de Transcrição NFATC
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos