NOD2-DN

Expression-ready ORF Clones

Alias: NLRC2, CARD15, IBD1, BLAU

Nucleotide-binding oligomerization domain containing 2
Caspase recruitment domain-containing protein 15

Dominant negative NOD2 (NOD2-DN) 

NOD2/CARD15 is an intracellular pattern-recognition protein involved in bacterial detection. Its expression is restricted to monocytes [1]. NOD2 is a general sensor of bacterial peptidoglycan (PGN). It recognizes the minimal bioactive fragment of PGN, called muramyl dipeptide, also known as MDP, a motif found in all PGNs [2].
This recognition event triggers a pro-inflammatory signaling cascade regulated by NF-kB. Mutations in NOD2 have been recently related to increased susceptibility to Crohn’s disease (CD). NOD2 deficiency increases TLR2-mediated activation of NF-κB resulting in a pro-inflammatory cytokine bias which could contribute to the overwhelming inflammation seen in CD [3,4]. Dominant negative NOD2 was generated by a L145P mutation. This single amino-acid substitution in the CARD (caspase-recruitment domain) of the NOD2 gene inhibited the ability of the downstream factor RICK (also called RIP2 and CARDIAK) to activate NF-κB [5].

References:

1. Ogura Y. et al., 2001. Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB. J Biol Chem. 276(7):4812-8.
2. Girardin SE. et al., 2003. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem. 278(11):8869-72.
3. Watanabe T. et al., 2004. NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat Immunol. 5(8):800-8.
4. Netea MG. et al., 2004. NOD2 mediates anti-inflammatory signals induced by TLR2 ligands: implications for Crohn’s disease. Eur J Immunol. 34(7):2052-9.
5. Tanabe T. et al. 2004. Regulatory regions and critical residues of NOD2 involved in muramyl dipeptide recognition EMBO J. 23(7): 1587-1597.