A novel CARD containing splice-isoform of CIITA regulates nitric oxide synthesis in dendritic cells
Protein & Cell
;
(12): 291-306, 2010.
Artigo
em Inglês
| WPRIM
| ID: wpr-757726
ABSTRACT
MHC class II expression is controlled mainly at transcriptional level by class II transactivator (CIITA), which is a non-DNA binding coactivator and serves as a master control factor for MHC class II genes expression. Here, we describe the function of a novel splice-isoform of CIITA, DC-expressed caspase inhibitory isoform of CIITA (or DC-CASPIC), and we show that the expression of DCCASPIC in DC is upregulated upon lipopolysaccharides (LPS) induction. DC-CASPIC localizes to mitochondria, and protein-protein interaction study demonstrates that DC-CASPIC interacts with caspases and inhibits its activity in DC. Consistently, DC-CASPIC suppresses caspases-induced degradation of nitric oxide synthase-2 (NOS2) and subsequently promotes the synthesis of nitric oxide (NO). NO is an essential regulatory molecule that modulates the capability of DC in stimulating T cell proliferation/activation in vitro; hence, overexpression of DC-CASPIC in DC enhances this stimulation. Collectively, our findings reveal that DC-CASPIC is a key molecule that regulates caspases activity and NO synthesis in DC.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Farmacologia
/
Técnicas In Vitro
/
Células Dendríticas
/
RNA Mensageiro
/
Dados de Sequência Molecular
/
Proteínas Nucleares
/
Sequência de Bases
/
Ativação Linfocitária
/
Linfócitos T
/
Transativadores
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Protein & Cell
Ano de publicação:
2010
Tipo de documento:
Artigo
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