Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Valosin-containing protein-regulated endoplasmic reticulum stress causes NOD2-dependent inflammatory responses

ABSTRACT: To detect novel NOD2 interaction partners in the context of IBD, immunoprecipitates from wildtype NOD2 and mutant NOD2 with IBD-causing variants were analyzed using LC-MS/MS.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Thomas Fröhlich

LAB HEAD: Thomas Fröhlich

PROVIDER: PXD031539 | Pride | 2025-03-05

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	File_Assignment.csv	Csv
	checksum.txt	Txt
	exp1_IBD_NOD2.wiff	Wiff
	exp1_IBD_NOD2.wiff.scan	Wiff
	exp1_IBD_NOD2_RIP2.wiff	Wiff

Items per page:

1 - 5 of 45

Publications

Valosin-containing protein-regulated endoplasmic reticulum stress causes NOD2-dependent inflammatory responses.

Ghalandary Maryam M Li Yue Y Fröhlich Thomas T Magg Thomas T Liu Yanshan Y Rohlfs Meino M Hollizeck Sebastian S Conca Raffaele R Schwerd Tobias T Uhlig Holm H HH Bufler Philip P Koletzko Sibylle S Muise Aleixo M AM Snapper Scott B SB Hauck Fabian F Klein Christoph C Kotlarz Daniel D

Scientific reports 20220310 1

NOD2 polymorphisms may affect sensing of the bacterial muramyl dipeptide (MDP) and trigger perturbed inflammatory responses. Genetic screening of a patient with immunodeficiency and enteropathy revealed a rare homozygous missense mutation in the first CARD domain of NOD2 (ENST00000300589; c.160G > A, p.E54K). Biochemical assays confirmed impaired NOD2-dependent signaling and proinflammatory cytokine production in patient's cells and heterologous cellular models with overexpression of the NOD2 mu ...[more]

PMID: 35273242

Similar Datasets

Changes of Muramyl Dipeptide in Intestinal and Extra-intestinal Diseases

Project description:Nucleotide-binding oligomerization domain 2 (Nod2) signaling is critical for human health.To figure out the clinical relevance of NOD2 ligands, the investigators plan to evaluate the change of NOD2 ligands in inflammatory bowel diseases (IBD), CRC, atherosclerotic cardiovascular disease (ACVD), and type 2 diabetes mellitus (DM2 ).

| 2380440 | ecrin-mdr-crc

Peptidoglycan metabolite photoaffinity reporters reveal direct binding to intracellular pattern recognition receptors and Arf GTPases

Project description:Extensive structure-activity studies of iE-DAP and MDP have demonstrated their selective activation of NOD1- and NOD2-expressing cells, respectively. Nonetheless, the direct binding of iE-DAP and MDP to NOD1 and NOD2, respectively, as well as other proteins in mammalian cells has not been systematically investigated. To address the direct interaction of iE-DAP and MDP with NOD1 and NOD2 in living cells, we synthesized a series of peptidoglycan metabolite photoaffinity chemical reporters containing a diazirine for photocrosslinking in cells and an alkyne tag for bioorthogonal detection of covalently-labeled proteins. The analysis of these peptidoglycan metabolite photoaffinity reporters demonstrate that iE-DAP and MDP can directly bind to NOD1 and NOD2 in mammalian cells. The crosslinking of these peptidoglycan metabolite photoaffinity reporters only occur with active variants of NOD1 and NOD2. Beyond direct binding to NOD2, the active MDP photoaffinity reporter selectively crosslinked Arf GTPases in NOD2-expressing cells and did so most prominently with GTP-bound Arf6, revealing the Arf proteins as novel direct pattern recognition receptors. Additional labeling and co-precipitation experiments suggest that MDP induces a complex between NOD2 and GTP-Arf6. This study highlights the utility of peptidoglycan metabolite photoaffinity reporters for characterizing their direct binding to intracellular pattern recognition receptors and identifying unpredicted cellular cofactors. The applications of these microbial-specific metabolite reporters should enable the discovery of other receptors, transporters and regulatory enzymes in host cells and microbes.

2020-05-26 | PXD012350 | Pride

Transcriptional profile in the colon in response to C. rodentium infection.

Project description:The identification of Atg16L1 as a susceptibility gene has implicated antibacterial autophagy in the pathogenesis of Crohn's disease, a major type of inflammatory bowel disease (IBD). However, the role of Atg16L1 during extracellular bacterial infections of the intestine has not been sufficiently examined and compared to the function of other IBD susceptibility genes such as Nod2. We now find that Atg16L1 mutant mice are extraordinarily resistant to intestinal disease induced by the model bacterial pathogen Citrobacter rodentium. We further demonstrate that Atg16L1 deficiency alters the intestinal environment to mediate an enhanced immune response that is dependent on monocytic cells, and that Atg16L1/Nod2 double mutant mice lose this advantage. These results reveal an unappreciated immuno-suppressive function of an IBD gene, and raise the possibility that gene variants that affect the autophagy pathway were evolutionarily maintained to protect against certain life-threatening infections.

2013-11-27 | GSE49109 | GEO

Transcriptional profile in the colon in response to C. rodentium infection.

2013-11-27 | E-GEOD-49109 | biostudies-arrayexpress

Gene expression analysis of PBMC's from IBD subjects stimulated by combinations of LPS, MDP, anti-CD3/anti-CD28 antibodies, and anti-IL10R antibodies.

Project description:We systematically investigated the transcriptomic response pattern of PBMC from 41 patients with IBD to characterize relevant stimuli that target different aspects of innate and adaptive immune cell responses. Lipopolysaccharide(LPS), muramyl-dipeptide (L18MDP), T cell receptor and co-stimulation (αCD3/αCD28 coated beads), and IL-10 signalling blockade were used to sitmulate subject PBMC's alone or in combination based on the concept that innate pathogen recognition receptor responses (in particular NOD2 and TLR4), T cell responses, and IL-10 signalling defects are implicated by multiple genetic IBD susceptibility loci and Mendelian forms of IBD.

2020-08-01 | GSE137680 | GEO

Pharmacological induction of selective endoplasmic reticulum retention as a novel strategy for cancer therapy

Project description:We analysed the difference in the surface proteome of human cells that were either subjected to ER stress (induced by thapsigargin (Tg)) only or were additionally treated with a pharmacological inhibitor against the eIF2α kinase PERK, which is localized in the endoplasmic reticulum. Compared to single ER stress, several important plasma-membrane associated kinases, showed a significant downregulation under PERK inhibition.

2020-03-02 | PXD014709 | Pride

E-MTAB-7915

Project description:PSC-IBD mucosal biology

2025-01-23 | E-MTAB-7915 | ExpressionAtlas

E. coli Affinity purification MS/MS

Project description:The tRNA linked repeat sequence rrB was tagged in either 5'- or 3'- end with the MS2 aptamer and expressed from a plasmid in E. coli. Using the MS2 aptamer, the RNAs were affinity purified after cell lysis. The co-purifying proteins were identified by NanoLC-MS/MS and compared to the proteins co-purifying with the MS2 sequence alone.

2021-04-26 | PXD013749 | Pride

The CLASP2 Protein Interaction Network in Adipocytes Links CLIP2 to AGAP3, CLASP2 to G2L1, MARK2, and SOGA1, and Identifies SOGA1 as a Microtubule-Associated Protein

Project description:CLASP2 is a microtubule-associated protein that undergoes insulin-stimulated phosphorylation and co-localization with reorganized actin and GLUT4 at the plasma membrane. To gain insight to the role of CLASP2 in this system, we developed and successfully executed a streamlined interactome approach and built a CLASP2 protein network in 3T3-L1 adipocytes. Using two different commercially available antibodies for CLASP2 and an antibody for epitope-tagged, overexpressed CLASP2, we performed multiple affinity purification coupled with mass spectrometry (AP-MS) experiments in combination with label-free quantitative proteomics and analyzed the data with the bioinformatics tool Significance Analysis of Interactome (SAINT). We discovered that CLASP2 co-immunoprecipitates (co-IPs) the novel protein SOGA1, the microtubule-associated protein kinase MARK2, and the microtubule/actin-regulating protein G2L1. The GTPase-activating proteins AGAP1 and AGAP3 were also enriched in the CLASP2 interactome, although subsequent AGAP3 and CLIP2 interactome analysis suggests a preference of AGAP3 for CLIP2. Follow-up MARK2 interactome analysis confirmed reciprocal co-IP of CLASP2 and also revealed MARK2 can co-IP SOGA1, glycogen synthase, and glycogenin. Investigating the SOGA1 interactome confirmed SOGA1 can reciprocal co-IP both CLASP2 and MARK2 as well as glycogen synthase and glycogenin. SOGA1 was confirmed to colocalize with CLASP2 and also with tubulin, which identifies SOGA1 as a new microtubule-associated protein. These results introduce the metabolic function of these proposed novel protein networks and their relationship with microtubules as new fields of cytoskeleton-associated protein biology.

2017-06-01 | PXD003674 | Pride

A phosphoproteomic approach reveals that PKD3 controls PKA-mediated glucose and tyrosine metabolism

Project description:Members of the Protein Kinase D (PKD) family (PKD1, 2, and 3) integrate hormonal and nutritional inputs to regulate complex cellular metabolism. Despite the fact that a number of functions have been annotated to particular PKDs, their molecular targets are relatively poorly explored. PKD3 promotes insulin sensitivity and suppresses lipogenesis in the liver of animals fed a high-fat diet. However, its substrates are largely unknown. Here we applied proteomic approaches to determine PKD3 targets. We identified over three-hundred putative targets of PKD3. Further, biochemical analysis revealed that PKD3 regulates cAMP-dependent protein kinase A (PKA) activity, a master regulator of the hepatic response to glucagon and fasting. PKA regulates glucose, lipid, and amino acid metabolism in the liver, by targeting key enzymes in the respective processes. Among them the PKA targets phenylalanine hydroxylase (PAH) catalyzes the conversion of phenylalanine to tyrosine Consistently, we showed that PKD3 is activated by glucagon and promotes glucose and tyrosine levels in hepatocytes

2021-06-17 | PXD026599 | Pride