Identification, evolution, and association study of a novel promoter and first exon of the human NOD2 (CARD15) gene

King, Kathy; Bagnall, Richard D.; Fisher, Sheila; Sheikh, Faisal; Cuthbert, Andrew; Tan, Seang‐Lin; Mundy, Nicholas I.; Rosenstiel, Philip; Schreiber, Stefan; Mathew, Christopher G.; Roberts, Roland G.

doi:10.1016/j.ygeno.2007.07.009

Cited by 5 publications

(3 citation statements)

References 33 publications

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“…1D). A second band of slightly smaller molecular size was also detectable that may correspond to smaller NOD2 isoforms (King et al, 2007;Leung et al, 2006;Ogura et al, 2001b).…”

Section: Cd147/emmprin Interacts With Nod2mentioning

confidence: 96%

A role for membrane-bound CD147 in NOD2-mediated recognition of bacterial cytoinvasion

Till

Rosenstiel

Bräutigam

et al. 2008

Journal of Cell Science

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NOD2 is an intracellular receptor for the bacterial cell wall component muramyl dipeptide. Mutations in the leucine-rich repeat region of NOD2, which lead to an impaired recognition of muramyl dipeptide, have been associated with chronic inflammatory diseases of barrier organs such as Crohn disease, asthma and atopic eczema. In this study we identify CD147 (also known as BSG and EMMPRIN), a membrane-bound regulator of cellular migration, differentiation and inflammatory processes, as a protein interaction partner of NOD2. We demonstrate a complex influence of the CD147-NOD2 interaction on NOD2-dependent signaling responses. We show that CD147 itself acts as an enhancer of the invasion of Listeria monocytogenes, an intracellular bacterial pathogen. We propose that the CD147-NOD2 interaction serves as a molecular guide to regulate NOD2 function at sites of pathogen invasion.

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“…1D). A second band of slightly smaller molecular size was also detectable that may correspond to smaller NOD2 isoforms (King et al, 2007;Leung et al, 2006;Ogura et al, 2001b).…”

Section: Cd147/emmprin Interacts With Nod2mentioning

confidence: 96%

A role for membrane-bound CD147 in NOD2-mediated recognition of bacterial cytoinvasion

Till

Rosenstiel

Bräutigam

et al. 2008

Journal of Cell Science

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“…Stimulation of NOD2 by ligand recognition triggers the recruitment of receptor‐interacting protein (RIP)2, which stimulates the NF‐κB and MAPK pathways through TRAF6, TAK‐1‐binding protein 2 – transforming growth factor‐β‐activated kinase 1 (TAK1), and IκB kinase (IKK) (Abbott et al ., 2007; Hasegawa et al ., 2008). Baseline expression of NOD2 in epithelial and myelomonocytic cells is low, and stimulation of the inflammatory cytokines and lipopolysaccharide (LPS) upregulates NOD2 expression via NF‐κB (Gutierrez et al ., 2002; King et al ., 2007). In RAW264.7 macrophages, two phases of expressional changes of NOD2 mRNAs, occurring at 2 and 8∼12 h after endotoxin treatment were, respectively, observed.…”

Section: Introductionmentioning

confidence: 99%

Dual roles of NOD2 in TLR4-mediated signal transduction and -induced inflammatory gene expression in macrophages

Tsai

Huang

et al. 2011

Cellular Microbiology

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SummaryNOD2 of the NLRs and TLR4 of the TLRs are major pattern-recognition receptors, which sense different microbial pathogens and have important roles in innate immunity. Herein, we investigated the roles of NOD2 in TLR4-mediated signalling and gene regulation in RAW264.7 macrophages. We found that MDP (a NOD2 ligand) increased LPSinduced expressions of TNF-a, IL-1b, IL-6, iNOS and COX-2. MDP did not affect LPS-induced activation of MAPKs or IKK, while it potentiated LPS-induced NF-kB activation. Meanwhile TLR4 activation increased NOD2 mRNA expression, and upregulated NOD2 upon MDP treatment is a positive regulator of TLR4-mediated signalling. Intriguingly we found that NOD2 silencing led to increases in LPSinduced signal transduction and inflammatory responses, and a decrease in LPS-elicited homologous tolerance. We thus propose that NOD2 in the absence of MDP treatment might also play a negative regulatory role in the action of TLR4. Further, we demonstrated that both CARD and LRR domains of the NOD2 protein were responsible for the negative regulatory action on TLR4. In summary, it is the first time to demonstrate that NOD2 have dual effects on TLR4 signalling and exert a novel ligandindependent action. Elucidating molecular mechanisms by which NOD2 exerts its ligand-independent action on TLR4 requires further investigation.

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“…NOD2-35 encoded only the first 25 N-terminal amino acid residues of NOD2, followed by a novel sequence of 10 amino acid residues [ 56 ]. A novel alternative promoter and novel first exon of NOD2 are responsible for producing a protein of 1023 amino acids, which is likely to be translated from the first ATG in exon 2 (known as Met28) [ 57 , 58 ]. In addition, five NOD2 variants are generated by alternatively spliced transcripts of the LRR domains [ 56 ].…”

Section: Alternative Splicing and Immune Function Of Nucleotide Bimentioning

confidence: 99%

Alternative Pre-mRNA Splicing in Mammals and Teleost Fish: A Effective Strategy for the Regulation of Immune Responses Against Pathogen Infection

Chang

Zhang

2017

IJMS

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Pre-mRNA splicing is the process by which introns are removed and the protein coding elements assembled into mature mRNAs. Alternative pre-mRNA splicing provides an important source of transcriptome and proteome complexity through selectively joining different coding elements to form mRNAs, which encode proteins with similar or distinct functions. In mammals, previous studies have shown the role of alternative splicing in regulating the function of the immune system, especially in the regulation of T-cell activation and function. As lower vertebrates, teleost fish mainly rely on a large family of pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs) from various invading pathogens. In this review, we summarize recent advances in our understanding of alternative splicing of piscine PRRs including peptidoglycan recognition proteins (PGRPs), nucleotide binding and oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) and their downstream signaling molecules, compared to splicing in mammals. We also discuss what is known and unknown about the function of splicing isoforms in the innate immune responses against pathogens infection in mammals and teleost fish. Finally, we highlight the consequences of alternative splicing in the innate immune system and give our view of important directions for future studies.

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Identification, evolution, and association study of a novel promoter and first exon of the human NOD2 (CARD15) gene

Cited by 5 publications

References 33 publications

A role for membrane-bound CD147 in NOD2-mediated recognition of bacterial cytoinvasion

A role for membrane-bound CD147 in NOD2-mediated recognition of bacterial cytoinvasion

Dual roles of NOD2 in TLR4-mediated signal transduction and -induced inflammatory gene expression in macrophages

Alternative Pre-mRNA Splicing in Mammals and Teleost Fish: A Effective Strategy for the Regulation of Immune Responses Against Pathogen Infection

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