NOD2-C2 - a novel NOD2 isoform activating NF-kappaB in a muramyl dipeptide-independent manner.

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Citation

Kramer M, Boeck J, Reichenbach D, Kaether C, Schreiber S, Platzer M, Rosenstiel P, Huse K

NOD2-C2 - a novel NOD2 isoform activating NF-kappaB in a muramyl dipeptide-independent manner.

BMC Res Notes. 2010 Aug 10;3:224. doi: 10.1186/1756-0500-3-224.

PubMed ID
20698950 [ View in PubMed
]
Abstract

BACKGROUND: The innate immune system employs several receptor families that form the basis of sensing pathogen-associated molecular patterns. NOD (nucleotide-binding and oligomerization domain) like receptors (NLRs) comprise a group of cytosolic proteins that trigger protective responses upon recognition of intracellular danger signals. NOD2 displays a tandem caspase recruitment domain (CARD) architecture, which is unique within the NLR family. FINDINGS: Here, we report a novel alternative transcript of the NOD2 gene, which codes for a truncated tandem CARD only protein, called NOD2-C2. The transcript isoform is highest expressed in leucocytes, a natural barrier against pathogen invasion, and is strictly linked to promoter usage as well as predominantly to one allele of the single nucleotide polymorphism rs2067085. Contrary to a previously identified truncated single CARD NOD2 isoform, NOD2-S, NOD2-C2 is able to activate NF-kappaB in a dose dependent manner independently of muramyl dipeptide (MDP). On the other hand NOD2-C2 competes with MDPs ability to activate the NOD2-driven NF-kappaB signaling cascade. CONCLUSION: NOD2 transcripts having included an alternative exon downstream of exon 3 (exon 3a) are the endogenous equivalents of a previously described in vitro construct with the putative protein composed of only the two N-terminal CARDs. This protein form (NOD2-C2) activates NF-kappaB independent of an MDP stimulus and is a potential regulator of NOD2 signaling.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Nucleotide-binding oligomerization domain-containing protein 2Q9HC29Details