ArticleMolecular and cellular biology2013
A discrete ubiquitin-mediated network regulates the strength of NOD2 signaling.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- The Role of Ubiquitin-Proteasome System (UPS) in Asthma Pathology.Journal of asthma and allergy · 2025Review
- Structure shows that the BIR2 domain of E3 ligase XIAP binds across the RIPK2 kinase dimer interface.Life science alliance · 2023Article
- NF-kB in Signaling Patterns and Its Temporal Dynamics Encode/Decode Human Diseases.Life (Basel, Switzerland) · 2022Review
- Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination.Viruses · 2021Review
- A regulatory region on RIPK2 is required for XIAP binding and NOD signaling activity.EMBO reports · 2020Article
- Itch regulation of innate and adaptive immune responses in mice and humans.Journal of leukocyte biology · 2020Review
- Unique BIR domain sets determine inhibitor of apoptosis protein-driven cell death and NOD2 complex signal specificity.Science signaling · 2018Article
- E3 Ubiquitin ligase ZNRF4 negatively regulates NOD2 signalling and induces tolerance to MDP.Nature communications · 2017Article
- Synthetic Biology Reveals the Uniqueness of the RIP Kinase Domain.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Ubiquitin in the activation and attenuation of innate antiviral immunity.The Journal of experimental medicine · 2016Review
- Inflammatory Signaling by NOD-RIPK2 Is Inhibited by Clinically Relevant Type II Kinase Inhibitors.Chemistry & biology · 2015Article
- An IκB Kinase-Regulated Feedforward Circuit Prolongs Inflammation.Cell reports · 2015Article
- International Union of Basic and Clinical Pharmacology. XCVI. Pattern recognition receptors in health and disease.Pharmacological reviews · 2015Review
- In vivo inhibition of RIPK2 kinase alleviates inflammatory disease.The Journal of biological chemistry · 2014Article
- The BIRC6 gene as a novel target for therapy of prostate cancer: dual targeting of inhibitors of apoptosis.Oncotarget · 2014Article
- RIP2 activity in inflammatory disease and implications for novel therapeutics.Journal of leukocyte biology · 2013Review
- Disease-causing mutations in the XIAP BIR2 domain impair NOD2-dependent immune signalling.EMBO molecular medicine · 2013Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Dysregulation of NOD2 signaling is implicated in the pathology of various inflammatory diseases, including Crohn's disease, asthma, and sarcoidosis, making signaling proteins downstream of NOD2 potential therapeutic targets. Inhibitor-of-apoptosis (IAP) proteins, particularly cIAP1, are essential mediators of NOD2 signaling, and in this work, we describe a molecular mechanism for cIAP1's regulation in the NOD2 signaling pathway. While cIAP1 promotes RIP2's tyrosine phosphorylation and subsequent NOD2 signaling, this positive regulation is countered by another E3 ubiquitin ligase, ITCH, through direct ubiquitination of cIAP1. This ITCH-mediated ubiquitination leads to cIAP1's lysosomal degradation. Pharmacologic inhibition of cIAP1 expression in ITCH(-/-) macrophages attenuates heightened ITCH(-/-) macrophage muramyl dipeptide-induced responses. Transcriptome analysis, combined with pharmacologic inhibition of cIAP1, further defines specific pathways within the NOD2 signaling pathway that are targeted by cIAP1. This information provides genetic signatures that may be useful in repurposing cIAP1-targeted therapies to correct NOD2-hyperactive states and identifies a ubiquitin-regulated signaling network centered on ITCH and cIAP1 that controls the strength of NOD2 signaling.
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Registered trials
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.