ArticleNature2014
A Crohn's disease variant in Atg16l1 enhances its degradation by caspase 3.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 231 papers, 5 of them syntheses that pooled it.
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Who cites it
231 citing papers in PubMed, 5 syntheses or guidelines pooled it, 361 citations in OpenAlex.
- Population stratified differences between ATG16L1 rs2241880 polymorphism with Crohn's disease risk: a systematic review and meta-analysis.BMC gastroenterology · 2025Pooled it
- ATG16L1 rs2241880/T300A increases susceptibility to perianal Crohn's disease: An updated meta-analysis on inflammatory bowel disease risk and clinical outcomes.United European gastroenterology journal · 2024Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target.Nature reviews. Drug discovery · 2020Pooled it
- Systematic review: gastrointestinal infection and incident inflammatory bowel disease.Alimentary pharmacology & therapeutics · 2020Pooled it
- Canonical and noncanonical autophagy in immunity.Immunity · 2026Review
- Emerging antimicrobial peptides in gastrointestinal disorders: Dual role in immunity and therapy.World journal of gastrointestinal pharmacology and therapeutics · 2026Review
- Variations in Autophagy-Related GenesCancers · 2026Article
- Terminal Ileal Ulcers: Endoscopic Predictors for the Later Development of Crohn's Disease.Diagnostics (Basel, Switzerland) · 2026Article
- Chronic enteritis triggered by diet westernization is driven by epithelial ATG16L1-mediated autophagy.Autophagy · 2026Article
- The Role of Traditional Chinese Medicine in Acute Lung Injury: Targeting Programmed Cell Death.Drug design, development and therapy · 2026Review
- Mitophagy in inflammatory bowel disease: regulatory mechanisms and therapeutic potential.Frontiers in cell and developmental biology · 2026Review
- Integrating the hallmarks of cancer into autophagy: a perspective from underlying mechanisms to therapeutic strategies.Theranostics · 2026Review
- SIRL-1 deficiency reveals pro-inflammatory IL-8 axis in inflammatory bowel disease: a novel diagnostic ratio.Frontiers in immunology · 2026Article
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- Development of an FKBP12-recruiting chemical-induced proximity DNA-encoded library and its application to discover an autophagy potentiator.Cell chemical biology · 2025Article
- Lysosomes finely control macrophage inflammatory function via regulating the release of lysosomal FeNature communications · 2025Article
- Autophagy and Bacterial infections.Autophagy reports · 2025Review
- Regulated programmed cell death in acute lung injury: from pathogenesis to therapy.Frontiers in immunology · 2025Review
171 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Crohn's disease is a debilitating inflammatory bowel disease (IBD) that can involve the entire digestive tract. A single-nucleotide polymorphism (SNP) encoding a missense variant in the autophagy gene ATG16L1 (rs2241880, Thr300Ala) is strongly associated with the incidence of Crohn's disease. Numerous studies have demonstrated the effect of ATG16L1 deletion or deficiency; however, the molecular consequences of the Thr300Ala (T300A) variant remains unknown. Here we show that amino acids 296-299 constitute a caspase cleavage motif in ATG16L1 and that the T300A variant (T316A in mice) significantly increases ATG16L1 sensitization to caspase-3-mediated processing. We observed that death-receptor activation or starvation-induced metabolic stress in human and murine macrophages increased degradation of the T300A or T316A variants of ATG16L1, respectively, resulting in diminished autophagy. Knock-in mice harbouring the T316A variant showed defective clearance of the ileal pathogen Yersinia enterocolitica and an elevated inflammatory cytokine response. In turn, deletion of the caspase-3-encoding gene, Casp3, or elimination of the caspase cleavage site by site-directed mutagenesis rescued starvation-induced autophagy and pathogen clearance, respectively. These findings demonstrate that caspase 3 activation in the presence of a common risk allele leads to accelerated degradation of ATG16L1, placing cellular stress, apoptotic stimuli and impaired autophagy in a unified pathway that predisposes to Crohn's disease.
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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.