%A Dachuan Huang, Sylvia Lim, Rong Yuan Ray Chua, Hong Shi, Siew Heng Wong, Mah Lee Ng %T A novel CARD containing splice-isoform of CIITA regulates nitric oxide synthesis in dendritic cells %0 Journal Article %D 2010 %J Protein Cell %J Protein & Cell %@ 1674-800X %R 10.1007/s13238-010-0039-5 %P 291-306 %V 1 %N 3 %U {https://journal.hep.com.cn/pac/EN/10.1007/s13238-010-0039-5 %8 2010-03-01 %X 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 DC-CASPIC 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.