Nod2, a Nod1/Apaf-1 Family Member That Is Restricted to Monocytes and Activates NF-κB*

By Y. Ogura, N. Inohara, A. Benito, Felicia F. Chen, S. Yamaoka, G. Núñez. Journal of Biological Chemistry, 2001

1,425 citations recorded by the source corpus.

Apaf-1 and Nod1 are members of a protein family, each of which contains a caspase recruitment domain (CARD) linked to a nucleotide-binding domain, which regulate apoptosis and/or NF-κB activation. Nod2, a third member of the family, was identified. Nod2 is composed of two N-terminal CARDs, a nucleotide-binding domain, and multiple C-terminal leucine-rich repeats. Although Nod1 and Apaf-1 were broadly expressed in tissues, the expression of Nod2 was highly restricted to monocytes. Nod2 induced nuclear factor κB (NF-κB) activation, which required IKKγ and was inhibited by dominant negative mutants of IκBα, IKKα, IKKβ, and IKKγ. Nod2 interacted with the serine-threonine kinase RICK via a homophilic CARD-CARD interaction. Furthermore, NF-κB activity induced by Nod2 correlated with its ability to interact with RICK and was specifically inhibited by a truncated mutant form of RICK containing its CARD. The identification of Nod2 defines a subfamily of Apaf-1-like proteins that function through RICK to activate a NF-κB signaling pathway.

Subfields: Immunology, Immunology and Allergy, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/801a7c28c7f713ad60060f3e03d08473d363e845

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. Shizuo Akira
2. J. Tschopp
3. R. Medzhitov
4. G. Núñez
5. Fabio Martinon
6. W. Strober
7. C. Nathan
8. R. Flavell

In Immunology and Allergy

1. R. Flavell
2. R. Medzhitov

In Molecular Biology

1. J. Tschopp
2. G. Núñez
3. Fabio Martinon
4. R. Medzhitov
5. R. Flavell
6. N. Warner
7. N. Inohara
8. P. Murray

Citations in the corpus

• A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease (2001, background): “NOD2 , a gene that encodes a protein with homology to plant disease resistance gene products is located in the peak region of linkage on chromosome 16 (ref”
• CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease. (2002, methodology): “The recent identification of CARD15 as a gene involved in susceptibility to CD (Hampe et al. 2001; Hugot et al. 2001; Ogura et al. 2001a) provides an opportunity to study the relationships between CARD15 genotype and phenotype in IBD.”
• NALPs: a novel protein family involved in inflammation (2003, background): “cgi?l=64127">NOD2 were identified as proteins with structural homology to the apoptosis regulator APAF-1 (Ref”
• NOD2 is a negative regulator of Toll-like receptor 2–mediated T helper type 1 responses (2004, background): “This is shown by the fact that when NOD2-transfected human embryonic kidney (HEK) 293 cells are exposed to MDP, NOD2 enters into CARD-CARD interactions with the serine-threonine kinase RICK, resulting in activation of the transcription factor NF-κ”
• To be, or not to be: NF-κB is the answer – role of Rel/NF-κB in the regulation of apoptosis (2003, background): “NOD1 and NOD2 activate the canonical NF-kB pathway in a RICK-dependent manner (Bertin et al., 1999; Geddes et al., 2001; Ogura et al., 2001; Kobayashi et al., 2002).”
• NOD1 and NOD2: signaling, host defense, and inflammatory disease. (2014, background): “This led to the discovery of NOD2, a closely related protein with an additional CARD (Ogura et al., 2001b).”
• Signalling pathways and molecular interactions of NOD1 and NOD2 (2006, background): “In both humans and mice, APCs such as macrophages and dendritic cells (DCs) express NOD1 and NOD2, whereas other haematopoietic cells (such as T cells and B cells) do not express these protein”