A novel CARD containing splice-isoform of CIITA regulates nitric oxide synthesis in dendritic cells.
10.1007/s13238-010-0039-5
- Author:
Dachuan HUANG
1
;
Sylvia LIM
;
Rong Yuan Ray CHUA
;
Hong SHI
;
Mah Lee NG
;
Siew Heng WONG
Author Information
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.
- Publication Type:Journal Article
- MeSH:
Alternative Splicing;
Amino Acid Sequence;
Animals;
Base Sequence;
CARD Signaling Adaptor Proteins;
genetics;
metabolism;
Cell Line;
Dendritic Cells;
drug effects;
immunology;
metabolism;
Humans;
In Vitro Techniques;
Lipopolysaccharides;
pharmacology;
Lymphocyte Activation;
Mice;
Mice, Inbred C57BL;
Mitochondria;
metabolism;
Molecular Sequence Data;
Nitric Oxide;
biosynthesis;
Nitric Oxide Synthase Type II;
metabolism;
Nuclear Proteins;
genetics;
metabolism;
Protein Isoforms;
genetics;
metabolism;
RNA, Messenger;
genetics;
metabolism;
T-Lymphocytes;
immunology;
metabolism;
Trans-Activators;
genetics;
metabolism;
Up-Regulation;
drug effects
- From:
Protein & Cell
2010;1(3):291-306
- CountryChina
- Language:English
-
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.
