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

doi:10.1007/s13238-010-0039-5

Protein Cell

2010, Vol. 1

Issue (3) : 291-306 https://doi.org/10.1007/s13238-010-0039-5 PMID: 21203976

Research articles

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

Dachuan Huang¹,Sylvia Lim¹,Rong Yuan Ray Chua¹,Hong Shi¹,Siew Heng Wong¹,Mah Lee Ng², ³,

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;

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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.

Keywords dendritic cells caspase CIITA nitric oxide synthase

Issue Date: 01 March 2010

Cite this article:

Dachuan Huang,Sylvia Lim,Rong Yuan Ray Chua, et al. A novel CARD containing splice-isoform of CIITA regulates nitric oxide synthesis in dendritic cells[J]. Protein Cell, 2010, 1(3): 291-306.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-010-0039-5
https://academic.hep.com.cn/pac/EN/Y2010/V1/I3/291

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