title: NOD2-C2 - a novel NOD2 isoform activating NF-kappaB in a muramyl dipeptide-independent manner.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Genome Analysis, Leibniz Institute for Age Research - Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany. mkramer@fli-leibniz.de.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kramer
authors.forename: Janne
authors.initials: J
authors.lastname: Boeck
authors.forename: Daniela
authors.initials: D
authors.lastname: Reichenbach
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaether
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Matthias
authors.initials: M
authors.lastname: Platzer
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
authors.forename: Klaus
authors.initials: K
authors.lastname: Huse