ArticleThe Journal of biological chemistry2014
The molecular chaperone HSP70 binds to and stabilizes NOD2, an important protein involved in Crohn disease.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Review
- Clinical description, genetic analysis and characterization of two NLRP12 heterozygous VUS variants.Frontiers in immunology · 2026Article
- A Novel Role of Neutrophil Elastase in Podocyte Dysfunction Induced by High Glucose, PMA, and MDP.Journal of cellular physiology · 2025Article
- Nucleotide-Binding Oligomerization Domain 2 in Signaling, Immunity, and Mycobacterial Infection.Immunity, inflammation and disease · 2025Review
- The Multiple Roles of Heat Shock Proteins in the Development of Inflammatory Bowel Disease.Current molecular medicine · 2025Review
- Role and molecular mechanism of NOD2 in chronic non-communicable diseases.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Inflammatory Bowel Diseases: An Updated Overview on the Heat Shock Protein Involvement.International journal of molecular sciences · 2023Review
- Multifaceted roles and regulation of nucleotide-binding oligomerization domain containing proteins.Frontiers in immunology · 2023Review
- Identification of a Multi-Messenger RNA Signature as Type 2 Diabetes Mellitus Candidate Genes Involved in Crosstalk between Inflammation and Insulin Resistance.Biomolecules · 2022Article
- Identification of Novel Endogenous NOD Ligands: Quantitative Analysis of Binding Affinities of NOD1 or NOD2 with Sphingosine-1-Phosphate Using Microscale Thermophoresis.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Triptolide inhibits migration and proliferation of fibroblasts from ileocolonic anastomosis of patients with Crohn's disease via regulating the miR‑16‑1/HSP70 pathway.Molecular medicine reports · 2019Article
- NOD Signaling and Cell Death.Frontiers in cell and developmental biology · 2019Review
- New use for CETSA: monitoring innate immune receptor stability via post-translational modification by OGT.Journal of bioenergetics and biomembranes · 2018Article
- NOD2 and inflammation: current insights.Journal of inflammation research · 2018Review
- Crohn's Disease Variants of Nod2 Are Stabilized by the Critical Contact Region of Hsp70.Biochemistry · 2017Article
- Membrane Association Dictates Ligand Specificity for the Innate Immune Receptor NOD2.ACS chemical biology · 2017Article
- Molecular Recognition of Muramyl Dipeptide Occurs in the Leucine-rich Repeat Domain of Nod2.ACS infectious diseases · 2017Article
- Understanding the regulation of pattern recognition receptors in inflammatory diseases - a 'Nod' in the right direction.Immunology · 2017Review
- The effect of NOD2 on the microbiota in Crohn's disease.Current opinion in biotechnology · 2016Review
- NLR-regulated pathways in cancer: opportunities and obstacles for therapeutic interventions.Cellular and molecular life sciences : CMLS · 2016Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Microbes are detected by the pathogen-associated molecular patterns through specific host pattern recognition receptors. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is an intracellular pattern recognition receptor that recognizes fragments of the bacterial cell wall. NOD2 is important to human biology; when it is mutated it loses the ability to respond properly to bacterial cell wall fragments. To determine the mechanisms of misactivation in the NOD2 Crohn mutants, we developed a cell-based system to screen for protein-protein interactors of NOD2. We identified heat shock protein 70 (HSP70) as a protein interactor of both wild type and Crohn mutant NOD2. HSP70 has previously been linked to inflammation, especially in the regulation of anti-inflammatory molecules. Induced HSP70 expression in cells increased the response of NOD2 to bacterial cell wall fragments. In addition, an HSP70 inhibitor, KNK437, was capable of decreasing NOD2-mediated NF-κB activation in response to bacterial cell wall stimulation. We found HSP70 to regulate the half-life of NOD2, as increasing the HSP70 level in cells increased the half-life of NOD2, and down-regulating HSP70 decreased the half-life of NOD2. The expression levels of the Crohn-associated NOD2 variants were less compared with wild type. The overexpression of HSP70 significantly increased NOD2 levels as well as the signaling capacity of the mutants. Thus, our study shows that restoring the stability of the NOD2 Crohn mutants is sufficient for rescuing the ability of these mutations to signal the presence of a bacterial cell wall ligand.
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