ArticleEndocrinology2014
Defective transport of the obesity mutant PC1/3 N222D contributes to loss of function.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 19 citations in OpenAlex.
- A domain-swapped proPC1/3 structure reveals a conformational checkpoint for ER export.bioRxiv : the preprint server for biology · 2026Article
- Analysis of Keratoconus-Related Phenotypes in Two Pcsk1 Mouse Models.Translational vision science & technology · 2026Article
- Pancreatic beta cell ER export in health and diabetes.Frontiers in endocrinology · 2023Review
- The G209R mutant mouse as a model for human PCSK1 polyendocrinopathy.Endocrinology · 2022Article
- Obesity, POMC, and POMC-processing Enzymes: Surprising Results From Animal Models.Endocrinology · 2021Review
- Mouse Models of Human Proprotein Convertase Insufficiency.Endocrine reviews · 2021Review
- Mice lacking PC1/3 expression in POMC-expressing cells do not develop obesity.Endocrinology · 2021Article
- A novel mutation in the mouse Pcsk1 gene showing obesity and diabetes.Mammalian genome : official journal of the International Mammalian Genome Society · 2020Article
- Reduced Stability and pH-Dependent Activity of a Common Obesity-Linked PCSK1 Polymorphism, N221D.Endocrinology · 2019Article
- Melanocortin 4 Receptor Pathway Dysfunction in Obesity: Patient Stratification Aimed at MC4R Agonist Treatment.The Journal of clinical endocrinology and metabolism · 2018Article
- Identification of a potential functional single nucleotide polymorphism for fatness and growth traits in the 3'-untranslated region of theJournal of animal science · 2017Article
- Endoplasmic reticulum-associated degradation of the mouse PC1/3-N222D hypomorph and human PCSK1 mutations contributes to obesity.International journal of obesity (2005) · 2016Article
- PCSK1 Variants and Human Obesity.Progress in molecular biology and translational science · 2016Review
- Revisiting PC1/3 Mutants: Dominant-Negative Effect of Endoplasmic Reticulum-Retained Mutants.Endocrinology · 2015Article
- Mechanism of Fine-tuning pH Sensors in Proprotein Convertases: IDENTIFICATION OF A pH-SENSING HISTIDINE PAIR IN THE PROPEPTIDE OF PROPROTEIN CONVERTASE 1/3.The Journal of biological chemistry · 2015Article
Corrections and comments
- Commented on by
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in the PCSK1 gene encoding prohormone convertase 1/3 (PC1/3) are strongly associated with obesity in humans. The PC1/3(N222D) mutant mouse thus far represents the only mouse model that mimics the PC1/3 obesity phenotype in humans. The present investigation addresses the cell biology of the N222D mutation. Metabolic labeling experiments reveal a clear defect in the kinetics of insulin biosynthesis in islets from PC1/3(N222D) mutant mice, resulting in an increase in both proinsulin and its processing intermediates, predominantly lacking cleavage at the Arg-Arg site. Although the mutant PC1/3 zymogen is correctly processed to the 87-kDa form, pulse-chase immunoprecipitation experiments, labeling, and immunohistochemical experiments using uncleavable variants all demonstrate that the PC1/3-N222D protein is largely mislocalized compared with similar wild-type (WT) constructs, being predominantly retained in the endoplasmic reticulum. The PC1/3-N222D mutant also undergoes more efficient degradation via the ubiquitin-proteasome system than the WT enzyme. Lastly, the mutant PC1/3-N222D protein coimmunoprecipitates with WT PC1/3 and exerts a modest effect on intracellular retention of the WT enzyme. These profound alterations in the cell biology of PC1/3-N222D are likely to contribute to the defective insulin biosynthetic events observed in the mutant mice and may be relevant to the dramatic contributions of polymorphisms in this gene to human obesity.
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.