ArticleCell death and differentiation2022
Palmitoylation restricts SQSTM1/p62-mediated autophagic degradation of NOD2 to modulate inflammation.
Article in Cell death and differentiation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- The role of palmitoylation modifications in the regulation of bone cell function, bone homeostasis, and osteoporosis.Bone & joint research · 2025Pooled it
- The role of protein palmitoylation in disease pathogenesis and therapeutic innovation.Annals of medicine · 2026Review
- ZDHHC5-mediated S-palmitoylation of NOD2 drives neutrophil extracellular trap formation via mitophagy to exacerbate inflammation in COPD.Biomarker research · 2026Article
- Review
- ZDHHC5: a pivotal palmitoyltransferase orchestrating signaling networks - unraveling mechanisms and therapeutic horizons.Biomarker research · 2026Review
- LL-37: Biological Mechanisms and Emerging Therapeutic Applications in Intestinal Disease.Immunity, inflammation and disease · 2026Review
- From lipid modification to cell death: the diverse roles of S-palmitoylation in cell fate decisions.Cell communication and signaling : CCS · 2026Review
- Review
- Lactucopicrin promotes the autophagic degradation of MAP2K4/MKK4 by mediating CCDC50 palmitoylation to alleviate osteoarthritis progression.Autophagy · 2026Article
- S-palmitoylation in ferroptosis: molecular mechanisms, modulators, and interplay with autophagy.Apoptosis : an international journal on programmed cell death · 2026Review
- The palmitoylation code in cell death signaling: from molecular mechanisms to therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Regulatory Landscapes of Protein Acylations in Neuroinflammation: From Molecular Mechanisms to Therapeutic Targets.Neurochemical research · 2025Review
- TRIM39 aggravates hepatocellular carcinoma growth through targeting the p62-KEAP1-NRF2 axis.Scientific reports · 2025Article
- Palmitoylation of TBK1 enhances the type I interferon signaling and strengthens anti-malarial immunity in mice.Nature communications · 2025Article
- In Vivo and In Vitro Antioxidant Effects ofAntioxidants (Basel, Switzerland) · 2025Article
- S-palmitoylation coordinates the trafficking of ATG9A to mediate autophagy initiation.Autophagy · 2025Article
- Identification of biomarkers and mechanisms associated with palmitoylation in acute kidney injury using transcriptome and single cell data.Scientific reports · 2025Article
- Palmitic acid and palmitoylation in cancer: Understanding, insights, and challenges.Innovation (Cambridge (Mass.)) · 2025Review
- Role of S-palmitoylation in digestive system diseases.Cell death discovery · 2025Review
- Straight A's: protein acylation in the S-activation and autophagic degradation of NOD-like receptors.Biochemical Society transactions · 2025Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nucleotide-binding oligomerization domain protein 2 (NOD2) senses bacterial peptidoglycan to induce proinflammatory and antimicrobial responses. Dysregulation of NOD2 signaling is involved in multiple inflammatory disorders. Recently, S-palmitoylation, a novel type of post-translational modification, is reported to play a crucial role in membrane association and ligand-induced signaling of NOD2, yet its influence on the stability of NOD2 is unclear. Here we show that inhibition of S-palmitoylation facilitates the SQSTM1/p62-mediated autophagic degradation of NOD2, while S-palmitoylation of NOD2 by ZDHHC5 promotes the stability of NOD2. Furthermore, we identify a gain-of-function R444C variant of NOD2 short isoform (NOD2s-R444C) in autoinflammatory disease, which induces excessive inflammation through its high S-palmitoylation level. Mechanistically, the NOD2s-R444C variant possesses a stronger binding ability to ZDHHC5, which promotes its S-palmitoylation, and restricts its autophagic degradation by reducing its interaction with SQSTM1/p62. Taken together, our study reveals the regulatory role of S-palmitoylation in controlling NOD2 stability through the crosstalk with autophagy, and provides insights into the association between dysfunctional S-palmitoylation and the occurrence of inflammatory diseases.
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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.