NOD1 is ubiquitously expressed, while NOD2 expression is restricted to monocytes, macrophages, dendritic cells, and intestinal Paneth cells (Inohara et al. 2005). NOD1 and NOD2 activation induces transcription of immune response genes, predominantly mediated by the proinflammatory transcriptional factor NFkappaB but also by AP-1 and Elk-1 (Inohara et al. 2005). NFkappaB translocates to the nucleus following release from IkappaB proteins. NOD1 and NOD2 signaling involves an interaction between their caspase-recruitment domain (CARD) and the CARD of the kinase RIPK2 (RIP2/RICK). This leads to the activation of the NFkappaB pathway and MAPK pathways (Windheim et al. 2007).<br>Activated NODs oligomerize via their NACHT domains, inducing physical proximity of RIP2 proteins that is believed to trigger their K63-linked polyubiquitination, facilitating recruitment of the TAK1 complex. RIP2 also recruits NEMO, bringing the TAK1 and IKK complexes into proximity, leading to NF-kappaB activation and activation of MAPK signaling. Recent studies have demonstrated that K63-linked regulatory ubiquitination of RIP2 is essential for the recruitment of TAK1 (Hasegawa et al. 2008, Hitosumatsu et al. 2008). As observed for toll-like receptor (TLR) signaling, ubiquitination can be removed by the deubiquitinating enzyme A20, thereby dampening NOD1/NOD2-induced NF-kappaB activation. NOD1 and NOD2 both induce K63-linked ubiquitination of RIP2, but NOD2-signaling appears to preferentially utilize the E3 ligase TRAF6, while TRAF2 and TRAF5 were shown to be important for NOD1-mediated signaling. In both cases, activation of NF-kappaB results in the upregulated transcription and production of inflammatory mediators. Authored: Jupe, S, 2010-04-22 Edited: Jupe, S, 2011-04-28 Reviewed: Wong, Edmond, 2011-06-06 Reviewed: Kufer, TA, 2011-04-28 Reviewed: Rittinger, K, 2011-06-06

http://purl.obolibrary.org/obo/HINO_0022297

NOD1 is ubiquitously expressed, while NOD2 expression is restricted to monocytes, macrophages, dendritic cells, and intestinal Paneth cells (Inohara et al. 2005). NOD1 and NOD2 activation induces transcription of immune response genes, predominantly mediated by the proinflammatory transcriptional factor NFkappaB but also by AP-1 and Elk-1 (Inohara et al. 2005). NFkappaB translocates to the nucleus following release from IkappaB proteins. NOD1 and NOD2 signaling involves an interaction between their caspase-recruitment domain (CARD) and the CARD of the kinase RIPK2 (RIP2/RICK). This leads to the activation of the NFkappaB pathway and MAPK pathways (Windheim et al. 2007).
Activated NODs oligomerize via their NACHT domains, inducing physical proximity of RIP2 proteins that is believed to trigger their K63-linked polyubiquitination, facilitating recruitment of the TAK1 complex. RIP2 also recruits NEMO, bringing the TAK1 and IKK complexes into proximity, leading to NF-kappaB activation and activation of MAPK signaling. Recent studies have demonstrated that K63-linked regulatory ubiquitination of RIP2 is essential for the recruitment of TAK1 (Hasegawa et al. 2008, Hitosumatsu et al. 2008). As observed for toll-like receptor (TLR) signaling, ubiquitination can be removed by the deubiquitinating enzyme A20, thereby dampening NOD1/NOD2-induced NF-kappaB activation. NOD1 and NOD2 both induce K63-linked ubiquitination of RIP2, but NOD2-signaling appears to preferentially utilize the E3 ligase TRAF6, while TRAF2 and TRAF5 were shown to be important for NOD1-mediated signaling. In both cases, activation of NF-kappaB results in the upregulated transcription and production of inflammatory mediators.

Authored: Jupe, S, 2010-04-22

Edited: Jupe, S, 2011-04-28

Reviewed: Wong, Edmond, 2011-06-06

Reviewed: Kufer, TA, 2011-04-28

Reviewed: Rittinger, K, 2011-06-06

Pubmed18079694

Pubmed18585455

Pubmed17348859

Reactome, http://www.reactome.org

Pubmed18342009

Pubmed18414735

Pubmed18928408

Pubmed15952891

NOD1/2 Signaling Pathway

http://purl.obolibrary.org/obo/NCBITaxon_9606

HINO:0022297

NOD1/2 Signaling Pathway

GENE ONTOLOGYGO:0070423

ReactomeREACT_75776

Reactome Database ID Release 43168638

http://purl.obolibrary.org/obo/INO_0000021

http://purl.obolibrary.org/obo/HINO_0008447

http://purl.obolibrary.org/obo/HINO_0008449

http://purl.obolibrary.org/obo/HINO_0008441

http://purl.obolibrary.org/obo/HINO_0008442

http://purl.obolibrary.org/obo/HINO_0008443

http://purl.obolibrary.org/obo/HINO_0008448

http://purl.obolibrary.org/obo/HINO_0008444

http://purl.obolibrary.org/obo/HINO_0008434

http://purl.obolibrary.org/obo/HINO_0008436

http://purl.obolibrary.org/obo/HINO_0008435

http://purl.obolibrary.org/obo/HINO_0026731

http://purl.obolibrary.org/obo/HINO_0008450

http://purl.obolibrary.org/obo/HINO_0008452

http://purl.obolibrary.org/obo/HINO_0008454

http://purl.obolibrary.org/obo/HINO_0008455

http://purl.obolibrary.org/obo/HINO_0008453

http://purl.obolibrary.org/obo/HINO_0008451