Research articles

A novel CARD containing splice-isoform of CIITA regulates nitric oxide synthesis in dendritic cells

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  • 1.Laboratory of Membrane Trafficking and Immunoregulation, Department of Microbiology, Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Block MD4, 5 Science Drive 2, Singapore 117597, Republic of Singapore; 2.Laboratory of Flavivirology, Department of Microbiology, Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Block MD4, 5 Science Drive 2, Singapore 117597, Republic of Singapore; 3.2010-10-22 15:43:31;

Published date: 01 Mar 2010

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 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.

Cite this article

Dachuan Huang, Sylvia Lim, Rong Yuan Ray Chua, Hong Shi, Siew Heng Wong, Mah Lee Ng . A novel CARD containing splice-isoform of CIITA regulates nitric oxide synthesis in dendritic cells[J]. Protein & Cell, 2010 , 1(3) : 291 -306 . DOI: 10.1007/s13238-010-0039-5

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