Malt1-induced cleavage of regnase-1 in CD4(+) helper T cells regulates immune activation.
Cell
; 153(5): 1036-49, 2013 May 23.
Article
en En
| MEDLINE
| ID: mdl-23706741
ABSTRACT
Regnase-1 (also known as Zc3h12a and MCPIP1) is an RNase that destabilizes a set of mRNAs, including Il6 and Il12b, through cleavage of their 3' UTRs. Although Regnase-1 inactivation leads to development of an autoimmune disease characterized by T cell activation and hyperimmunoglobulinemia in mice, the mechanism of Regnase-1-mediated immune regulation has remained unclear. We show that Regnase-1 is essential for preventing aberrant effector CD4(+) T cell generation cell autonomously. Moreover, in T cells, Regnase-1 regulates the mRNAs of a set of genes, including c-Rel, Ox40, and Il2, through cleavage of their 3' UTRs. Interestingly, T cell receptor (TCR) stimulation leads to cleavage of Regnase-1 at R111 by Malt1/paracaspase, freeing T cells from Regnase-1-mediated suppression. Furthermore, Malt1 protease activity is critical for controlling the mRNA stability of T cell effector genes. Collectively, these results indicate that dynamic control of Regnase-1 expression in T cells is critical for controlling T cell activation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ribonucleasas
/
Activación de Linfocitos
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Linfocitos T Colaboradores-Inductores
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Caspasas
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Proteínas de Neoplasias
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell
Año:
2013
Tipo del documento:
Article
País de afiliación:
Japón