ArticleThe Journal of biological chemistry2017
Nucleotide-binding oligomerization domain (NOD) signaling defects and cell death susceptibility cannot be uncoupled in X-linked inhibitor of apoptosis (XIAP)-driven inflammatory disease.
Article in The Journal of biological chemistry, 2017. 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, 29 citations in OpenAlex.
- Monogenic forms of inflammatory bowel disease: Genetic mechanisms, models, and clinical implications.Molecular medicine (Cambridge, Mass.) · 2026Review
- Host-pathobiont interactions in Crohn's disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- Investigation of Oxidative-Stress Impact on Human Osteoblasts During Orthodontic Tooth Movement Using an In Vitro Tension Model.International journal of molecular sciences · 2024Article
- Investigation of Impact of Oxidative Stress on Human Periodontal Ligament Cells Exposed to Static Compression.International journal of molecular sciences · 2024Article
- Mediator kinase inhibition impedes transcriptional plasticity and prevents resistance to ERK/MAPK-targeted therapy in KRAS-mutant cancers.NPJ precision oncology · 2024Article
- Mediator Kinase Inhibition Impedes Transcriptional Plasticity and Prevents Resistance to ERK/MAPK-Targeted Therapy in KRAS-Mutant Cancers.Research square · 2023Article
- Effect of Different Parameters of In Vitro Static Tensile Strain on Human Periodontal Ligament Cells Simulating the Tension Side of Orthodontic Tooth Movement.International journal of molecular sciences · 2022Article
- Targeting RIP Kinases in Chronic Inflammatory Disease.Biomolecules · 2021Review
- Gasdermin E permits interleukin-1 beta release in distinct sublytic and pyroptotic phases.Cell reports · 2021Article
- The Growing Need to Understand Very Early Onset Inflammatory Bowel Disease.Frontiers in immunology · 2021Review
- Human polymorphisms in GSDMD alter the inflammatory response.The Journal of biological chemistry · 2020Article
- Review
- TNFR2 induced priming of the inflammasome leads to a RIPK1-dependent cell death in the absence of XIAP.Cell death & disease · 2019Article
- Harnessing the potential of gene editing technology using CRISPR in inflammatory bowel disease.World journal of gastroenterology · 2019Review
- Missense variants in NOX1 and p22phox in a case of very-early-onset inflammatory bowel disease are functionally linked to NOD2.Cold Spring Harbor molecular case studies · 2019Article
- Small molecule inhibitors reveal an indispensable scaffolding role of RIPK2 in NOD2 signaling.The EMBO journal · 2018Article
- Chemical disruption of the pyroptotic pore-forming protein gasdermin D inhibits inflammatory cell death and sepsis.Science immunology · 2018Article
- Unique BIR domain sets determine inhibitor of apoptosis protein-driven cell death and NOD2 complex signal specificity.Science signaling · 2018Article
- NOD2 and inflammation: current insights.Journal of inflammation research · 2018Review
- Recent advances in understanding inhibitor of apoptosis proteins.F1000Research · 2018Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The X-linked inhibitor of apoptosis (XIAP) protein has been identified as a key genetic driver of two distinct inflammatory disorders, X-linked lymphoproliferative syndrome 2 (XLP-2) and very-early-onset inflammatory bowel disease (VEO-IBD). Molecularly, the role of XIAP mutations in the pathogenesis of these disorders is unclear. Recent work has consistently shown XIAP to be critical for signaling downstream of the Crohn's disease susceptibility protein nucleotide-binding oligomerization domain-containing 2 (NOD2); however, the reported effects of XLP-2 and VEO-IBD XIAP mutations on cell death have been inconsistent. In this manuscript, we describe a CRISPR-mediated genetic system for cells of the myeloid lineage in which XIAP alleles can be replaced with disease-associated XIAP variants expressed at endogenous levels to simultaneously study inflammation-related cell death and NOD2 signaling. We show that, consistent with previous studies, NOD2 signaling is critically dependent on the BIR2 domain of XIAP. We further used this system to reconcile the aforementioned inconsistent XIAP cell death data to show that XLP-2 and VEO-IBD XIAP mutations that exhibit a loss-of-function NOD2 phenotype also lower the threshold for inflammatory cell death. Last, we identified and studied three novel patient XIAP mutations and used this system to characterize NOD2 and cell death phenotypes driven by XIAP. The results of this work support the role of XIAP in mediating NOD2 signaling while reconciling the role of XLP-2 and VEO-IBD XIAP mutations in inflammatory cell death and provide a set of tools and framework to rapidly test newly discovered XIAP variants.
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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.