ArticleGastroenterology2012
The nucleotide synthesis enzyme CAD inhibits NOD2 antibacterial function in human intestinal epithelial cells.
Article in Gastroenterology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- The emerging roles of glutamine amidotransferases in metabolism and immune defense.Nucleosides, nucleotides & nucleic acids · 2024Review
- Topical N-phosphonacetyl-l-aspartate is a dual action candidate for treating non-melanoma skin cancer.Experimental dermatology · 2023Article
- Anti-apoptotic genes and non-coding RNAs are potential outcome predictors for ulcerative colitis.Functional & integrative genomics · 2023Article
- Pyrimidine Biosynthetic Enzyme CAD: Its Function, Regulation, and Diagnostic Potential.International journal of molecular sciences · 2021Review
- IL-6 effector function of group 2 innate lymphoid cells (ILC2) is NOD2 dependent.Science immunology · 2021Article
- Review
- Urea Cycle Dysregulation Generates Clinically Relevant Genomic and Biochemical Signatures.Cell · 2018Article
- Pyrimidine synthesis inhibition enhances cutaneous defenses against antibiotic resistant bacteria through activation of NOD2 signaling.Scientific reports · 2018Article
- NOD2 and inflammation: current insights.Journal of inflammation research · 2018Review
- Urinary metabolic insights into host-gut microbial interactions in healthy and IBD children.World journal of gastroenterology · 2017Article
- Understanding the regulation of pattern recognition receptors in inflammatory diseases - a 'Nod' in the right direction.Immunology · 2017Review
- Urinary Metabolic Phenotyping Reveals Differences in the Metabolic Status of Healthy and Inflammatory Bowel Disease (IBD) Children in Relation to Growth and Disease Activity.International journal of molecular sciences · 2016Article
- Novel CAD-ALK gene rearrangement is drugable by entrectinib in colorectal cancer.British journal of cancer · 2015Article
- Blau syndrome-associated Nod2 mutation alters expression of full-length NOD2 and limits responses to muramyl dipeptide in knock-in mice.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Insights into the molecular basis of the NOD2 signalling pathway.Open biology · 2014Review
- A genome-wide small interfering RNA (siRNA) screen reveals nuclear factor-κB (NF-κB)-independent regulators of NOD2-induced interleukin-8 (IL-8) secretion.The Journal of biological chemistry · 2014Article
- The molecular chaperone HSP70 binds to and stabilizes NOD2, an important protein involved in Crohn disease.The Journal of biological chemistry · 2014Article
- Muramyl dipeptide responsive pathways in Crohn's disease: from NOD2 and beyond.Cellular and molecular life sciences : CMLS · 2013Review
- A genome-wide siRNA screen reveals positive and negative regulators of the NOD2 and NF-κB signaling pathways.Science signaling · 2013Article
- A dual role for receptor-interacting protein kinase 2 (RIP2) kinase activity in nucleotide-binding oligomerization domain 2 (NOD2)-dependent autophagy.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsPolymorphisms that reduce the function of nucleotide-binding oligomerization domain (NOD)2, a bacterial sensor, have been associated with Crohn's disease (CD). No proteins that regulate NOD2 activity have been identified as selective pharmacologic targets. We sought to discover regulators of NOD2 that might be pharmacologic targets for CD therapies.
methodsCarbamoyl phosphate synthetase/aspartate transcarbamylase/dihydroorotase (CAD) is an enzyme required for de novo pyrimidine nucleotide synthesis; it was identified as a NOD2-interacting protein by immunoprecipitation-coupled mass spectrometry. CAD expression was assessed in colon tissues from individuals with and without inflammatory bowel disease by immunohistochemistry. The interaction between CAD and NOD2 was assessed in human HCT116 intestinal epithelial cells by immunoprecipitation, immunoblot, reporter gene, and gentamicin protection assays. We also analyzed human cell lines that express variants of NOD2 and the effects of RNA interference, overexpression and CAD inhibitors.
resultsCAD was identified as a NOD2-interacting protein expressed at increased levels in the intestinal epithelium of patients with CD compared with controls. Overexpression of CAD inhibited NOD2-dependent activation of nuclear factor κB and p38 mitogen-activated protein kinase, as well as intracellular killing of Salmonella. Reduction of CAD expression or administration of CAD inhibitors increased NOD2-dependent signaling and antibacterial functions of NOD2 variants that are and are not associated with CD.
conclusionsThe nucleotide synthesis enzyme CAD is a negative regulator of NOD2. The antibacterial function of NOD2 variants that have been associated with CD increased in response to pharmacologic inhibition of CAD. CAD is a potential therapeutic target for CD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.