ArticleThe Journal of biological chemistry2016
A Carboxyl Ester Lipase (CEL) Mutant Causes Chronic Pancreatitis by Forming Intracellular Aggregates That Activate Apoptosis.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
- Mutations in the pancreatic secretory enzymesProceedings of the National Academy of Sciences of the United States of America · 2018Trial
- Article
- Characterization of a PNLIP variant identified in Amish pediatric patients with congenital pancreatic lipase deficiency.Journal of lipid research · 2025Article
- Omics research in atherosclerosis.Molecular and cellular biochemistry · 2025Review
- Misfolding PRSS1 variant p.Ala61Val in a case of suspected intrauterine pancreatitis.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2025Article
- Circulating pancreatic enzyme levels are a causal biomarker of type 1 diabetes.medRxiv : the preprint server for health sciences · 2024Article
- Current views on etiology, diagnosis, epidemiology and gene therapy of maturity onset diabetes in the young.Frontiers in endocrinology · 2024Review
- Characterization of novel PNLIP variants in congenital pancreatic lipase deficiency.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2023Article
- Article
- From glucose sensing to exocytosis: takes from maturity onset diabetes of the young.Frontiers in endocrinology · 2023Review
- A novel lipid metabolism gene signature for clear cell renal cell carcinoma using integrated bioinformatics analysis.Frontiers in cell and developmental biology · 2023Article
- Novel p.G250A Mutation Associated with Chronic Pancreatitis Highlights Misfolding-Prone Region in Carboxypeptidase A1 (CPA1).International journal of molecular sciences · 2022Article
- The genetic risk factor CEL-HYB1 causes proteotoxicity and chronic pancreatitis in mice.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2022Article
- Endoplasmic stress-inducing variants in carboxyl ester lipase and pancreatic cancer risk.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2022Article
- Maturity-Onset Diabetes of the Young: Mutations, Physiological Consequences, and Treatment Options.Journal of personalized medicine · 2022Review
- The ciliary protein Spef2 stimulates acinar Ampkα/Sirt1 signaling and ameliorates acute pancreatitis and associated lung injury.Annals of translational medicine · 2022Article
- Misfolding-induced chronic pancreatitis in CPA1 N256K mutant mice is unaffected by global deletion of Ddit3/Chop.Scientific reports · 2022Article
- Two New Mutations in the CEL Gene Causing Diabetes and Hereditary Pancreatitis: How to Correctly Identify MODY8 Cases.The Journal of clinical endocrinology and metabolism · 2022Article
- The CEL-HYB1 Hybrid Allele Promotes Digestive Enzyme Misfolding and Pancreatitis in Mice.Cellular and molecular gastroenterology and hepatology · 2022Article
- Abnormal exocrine-endocrine cell cross-talk promotes β-cell dysfunction and loss in MODY8.Nature metabolism · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Patients with chronic pancreatitis (CP) frequently have genetic risk factors for disease. Many of the identified genes have been connected to trypsinogen activation or trypsin inactivation. The description of CP in patients with mutations in the variable number of tandem repeat (VNTR) domain of carboxyl ester lipase (CEL) presents an opportunity to study the pathogenesis of CP independently of trypsin pathways. We tested the hypothesis that a deletion and frameshift mutation (C563fsX673) in the CEL VNTR causes CP through proteotoxic gain-of-function activation of maladaptive cell signaling pathways including cell death pathways. HEK293 or AR42J cells were transfected with constructs expressing CEL with 14 repeats in the VNTR (CEL14R) or C563fsX673 CEL (CEL maturity onset diabetes of youth with a deletion mutation in the VNTR (MODY)). In both cell types, CEL MODY formed intracellular aggregates. Secretion of CEL MODY was decreased compared with that of CEL14R. Expression of CEL MODY increased endoplasmic reticulum stress, activated the unfolded protein response, and caused cell death by apoptosis. Our results demonstrate that disorders of protein homeostasis can lead to CP and suggest that novel therapies to decrease the intracellular accumulation of misfolded protein may be successful in some patients with CP.
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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 Socratic graph.