negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway
Definition
Target type: biologicalprocess
Any process that stops, prevents, or reduces the frequency, rate, or extent of the nucleotide-binding oligomerization domain containing 2 (NOD2) pathway. [GOC:add]
Negative regulation of NOD2 signaling pathway involves a complex interplay of cellular mechanisms designed to fine-tune the immune response to bacterial and viral infections. NOD2, a pattern recognition receptor, senses muramyl dipeptide (MDP), a component of bacterial peptidoglycan. Upon MDP binding, NOD2 undergoes oligomerization, leading to the activation of downstream signaling pathways, including the NF-κB and MAPK pathways, culminating in the production of pro-inflammatory cytokines. However, excessive NOD2 signaling can be detrimental, leading to inflammatory diseases. Therefore, cells employ various strategies to dampen NOD2 signaling.
One mechanism involves the recruitment of negative regulators, such as A20 and CYLD, to the NOD2 signaling complex. These deubiquitinases remove ubiquitin modifications from signaling proteins, preventing their activation and downstream signaling. Additionally, protein phosphatases, such as PP2A, can dephosphorylate signaling components, further suppressing NOD2 signaling.
Another level of regulation involves the modulation of NOD2 expression. MicroRNAs, small non-coding RNA molecules, can bind to the 3' untranslated region (UTR) of NOD2 mRNA, inhibiting its translation and reducing NOD2 protein levels. Furthermore, post-translational modifications, such as phosphorylation and ubiquitination, can influence the stability and activity of NOD2.
Finally, the cellular environment plays a crucial role in regulating NOD2 signaling. Factors like cellular stress, oxidative stress, and the presence of specific metabolites can influence the activation and downstream signaling of NOD2.
In summary, negative regulation of NOD2 signaling involves a multifaceted interplay of molecular mechanisms, including the recruitment of negative regulators, modulation of NOD2 expression, post-translational modifications, and environmental factors, all aimed at maintaining a delicate balance between immune activation and cellular homeostasis.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Tyrosine-protein phosphatase non-receptor type 22 | A tyrosine-protein phosphatase non-receptor type 22 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y2R2] | Homo sapiens (human) |
Compounds (9)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| lawsone | lawsone : 1,4-Naphthoquinone carrying a hydroxy function at C-2. It is obtained from the leaves of Lawsonia inermis. lawsone: a molluscacide from leaves of Lawsonia inermis L. topical sunscreening agent; structure; powdered leaves of Lawsonia inermis(Lythraceae) used as brown hair dye | ||
| 1,2-naphthoquinone | 1,2-naphthoquinone : The parent structure of the family of 1,2-naphthoquinones, in which the oxo groups of the quinone moiety are at positions 1 and 2 of the naphthalene ring. It is a metabolite of naphthalene and is found in diesel exhaust particles. naphthalene-1,2-dione: structure given in first source | 1,2-naphthoquinones | aryl hydrocarbon receptor agonist; carcinogenic agent |
| 1,2-dihydroxynaphthalene | 1,2-dihydroxynaphthalene: RN given refers to parent cpd | naphthalenediol | mouse metabolite |
| cefsulodin | cefsulodin : A pyridinium-substituted semi-synthetic, broad-spectrum, cephalosporin antibiotic. Cefsulodin: A pyridinium-substituted semisynthetic, broad-spectrum antibacterial used especially for Pseudomonas infections in debilitated patients. | cephalosporin; organosulfonic acid; primary carboxamide | antibacterial drug |
| morusin | morusin : An extended flavonoid that is flavone substituted by hydroxy groups at positions 5, 2' and 4', a prenyl group at position 3 and a 2,2-dimethyl pyran group across positions 7 and 8. morusin: from Morus root bark; structure given in first source | extended flavonoid; trihydroxyflavone | antineoplastic agent; plant metabolite |
| trans-2,3',4,5'-tetrahydroxystilbene | trans-2,3',4,5'-tetrahydroxystilbene: hydroxystilbene oxyresveratrol | stilbenoid | |
| Norartocarpetin | flavones | ||
| cudraflavanone a | cudraflavanone A: antineoplastic from Cudrania tricuspidata; structure in first source | ||
| 3-(1-(3-(biphenyl-4-ylamino)-3-oxopropyl)-1h-1,2,3-triazol-4-yl)-6-hydroxy-1-methyl-2-phenyl-1h-indole-5-carboxylic acid | 3-(1-(3-(biphenyl-4-ylamino)-3-oxopropyl)-1H-1,2,3-triazol-4-yl)-6-hydroxy-1-methyl-2-phenyl-1H-indole-5-carboxylic acid: an SHP2 inhibitor; structure in first source |