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.He...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.展开更多
基金the Academic Research Council-Singapore Ministry of Education(R182-000-099-112 to S.H.W)NMRC(R182-000-137-213 to S.H.W)grants.
文摘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.
