ArticleEMBO molecular medicine2013
Disease-causing mutations in the XIAP BIR2 domain impair NOD2-dependent immune signalling.
Article in EMBO molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
89 citing papers in PubMed, 150 citations in OpenAlex.
- Mutation spectrum of NOD2 reveals recessive inheritance as a main driver of Early Onset Crohn's Disease.Scientific reports · 2021Trial
- USP25 augments XIAP-mediated signaling to safeguard intestinal homeostasis.Cell death and differentiation · 2026Article
- Monogenic disorders of the TNF signalling pathway.Nature reviews. Rheumatology · 2026Review
- Nucleotide-Binding Oligomerization Domain 2 in Signaling, Immunity, and Mycobacterial Infection.Immunity, inflammation and disease · 2025Review
- Genetic analysis of a female patient with X-linked lymphoproliferative disease type 2: a case report.Journal of medical case reports · 2025Article
- Autophagy in Disease Onset and Progression.Aging and disease · 2024Review
- Understanding the molecular mechanism of pathogenic variants of BIR2 domain in XIAP-deficient inflammatory bowel disease.Scientific reports · 2024Article
- NOD2-mediated dual negative regulation of inflammatory responses triggered by TLRs in the gastrointestinal tract.Frontiers in immunology · 2024Review
- Salvage Therapy and Allogeneic Hematopoietic Cell Transplantation for the Severe Cytokine Storm Syndrome of Hemophagocytic Lymphohistiocytosis.Advances in experimental medicine and biology · 2024Review
- Structure shows that the BIR2 domain of E3 ligase XIAP binds across the RIPK2 kinase dimer interface.Life science alliance · 2023Article
- The mechanism of linear ubiquitination in regulating cell death and correlative diseases.Cell death & disease · 2023Review
- X-linked inhibitor of apoptosis protein is a prognostic marker for a favorable outcome in three identified subsets in resectable adenocarcinoma of the pancreas.Journal of cancer research and clinical oncology · 2023Article
- Novel XIAP mutation with early-onset Crohn's disease complicated with acute heart failure: a case report.BMC cardiovascular disorders · 2023Article
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- When to suspect inborn errors of immunity in Epstein-Barr virus-related lymphoproliferative disorders.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2023Review
- Lentiviral Gene Transfer Corrects Immune Abnormalities in XIAP Deficiency.Journal of clinical immunology · 2023Article
- Paneth cell development in the neonatal gut: pathway regulation, development, and relevance to necrotizing enterocolitis.Frontiers in cell and developmental biology · 2023Review
- Human ZBP1 induces cell death-independent inflammatory signaling via RIPK3 and RIPK1.EMBO reports · 2022Article
- Epstein Barr virus-mediated transformation of B cells from XIAP-deficient patients leads to increased expression of the tumor suppressor CADM1.Cell death & disease · 2022Article
- Increased migration and motility in XIAP-null cells mediated by the C-RAF protein kinase.Scientific reports · 2022Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
X-linked Inhibitor of Apoptosis (XIAP) is an essential ubiquitin ligase for pro-inflammatory signalling downstream of the nucleotide-binding oligomerization domain containing (NOD)-1 and -2 pattern recognition receptors. Mutations in XIAP cause X-linked lymphoproliferative syndrome type-2 (XLP2), an immunodeficiency associated with a potentially fatal deregulation of the immune system, whose aetiology is not well understood. Here, we identify the XIAP baculovirus IAP repeat (BIR)2 domain as a hotspot for missense mutations in XLP2. We demonstrate that XLP2-BIR2 mutations severely impair NOD1/2-dependent immune signalling in primary cells from XLP2 patients and in reconstituted XIAP-deficient cell lines. XLP2-BIR2 mutations abolish the XIAP-RIPK2 interaction resulting in impaired ubiquitylation of RIPK2 and recruitment of linear ubiquitin chain assembly complex (LUBAC) to the NOD2-complex. We show that the RIPK2 binding site in XIAP overlaps with the BIR2 IBM-binding pocket and find that a bivalent Smac mimetic compound (SMC) potently antagonises XIAP function downstream of NOD2 to limit signalling. These findings suggest that impaired immune signalling in response to NOD1/2 stimulation is a general defect in XLP2 and demonstrate that the XIAP BIR2-RIPK2 interaction may be targeted pharmacologically to modulate inflammatory signalling.
Indexed as
Identifiers
What OpenQuestion holds
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.