ArticleEndocrinology2015
Revisiting PC1/3 Mutants: Dominant-Negative Effect of Endoplasmic Reticulum-Retained Mutants.
Article in Endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Effectiveness and Safety of Setmelanotide in a Patient With a Heterozygous PCSK1 Deficiency.Obesity (Silver Spring, Md.) · 2026Article
- A domain-swapped proPC1/3 structure reveals a conformational checkpoint for ER export.bioRxiv : the preprint server for biology · 2026Article
- Towards a genetic obesity risk score in a single-center study of children and adolescents with obesity.Scientific reports · 2025Article
- Prolonged stress alters the PC1/PC2 ratio in the rat lateral hypothalamus, implicating impaired orexin maturation.Iranian journal of basic medical sciences · 2024Article
- SERCA2 regulates proinsulin processing and processing enzyme maturation in pancreatic beta cells.Diabetologia · 2023Article
- Article
- Brain functional and structural magnetic resonance imaging of obesity and weight loss interventions.Molecular psychiatry · 2023Review
- The G209R mutant mouse as a model for human PCSK1 polyendocrinopathy.Endocrinology · 2022Article
- Mouse Models of Human Proprotein Convertase Insufficiency.Endocrine reviews · 2021Review
- Molecular evolution of PCSK family: Analysis of natural selection rate and gene loss.PloS one · 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
- Heterogeneous Expression of Proinsulin Processing Enzymes in Beta Cells of Non-diabetic and Type 2 Diabetic Humans.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2019Article
- Identification of a potential functional single nucleotide polymorphism for fatness and growth traits in the 3'-untranslated region of theJournal of animal science · 2017Article
- Functional analysis of PCSK2 coding variants: A founder effect in the Old Order Amish population.Diabetes research and clinical practice · 2017Article
- Functional and clinical relevance of novel and knownMolecular metabolism · 2017Article
- PCSK1 Variants and Human Obesity.Progress in molecular biology and translational science · 2016Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Prohormone convertase 1/3 (PC1/3), encoded by the gene PCSK1, is critical for peptide hormone synthesis. An increasing number of studies have shown that inactivating mutations in PCSK1 are correlated with endocrine pathologies ranging from intestinal dysfunction to morbid obesity, whereas the common nonsynonymous polymorphisms rs6232 (N221D) and rs6234-rs6235 (Q665E-S690T) are highly associated with obesity risk. In this report, we revisited the biochemical and cellular properties of PC1/3 variants in the context of a wild-type PC1/3 background instead of the S357G hypermorph background used for all previous studies. In the wild-type background the PC1/3 N221D variant exhibited 30% lower enzymatic activity in a fluorogenic assay than wild-type PC1/3; this inhibition was greater than that detected in an equivalent experiment using the PC1/3 S357G background. A PC1/3 variant with the linked carboxyl-terminal polymorphisms Q665E-S690T did not show this difference. We also analyzed the biochemical properties of 2 PC1/3 mutants, G209R and G593R, which are retained in the endoplasmic reticulum (ER), and studied their effects on wild-type PC1/3. The expression of ER-retained mutants induced ER stress markers and also resulted in dominant-negative blockade of wild-type PC1/3 prodomain cleavage and decreased expression of wild-type PC1/3, suggesting facilitation of the entry of wild-type protein to a degradative proteasomal pathway. Dominant-negative effects of PC1/3 mutations on the expression and maturation of wild-type protein, with consequential effects on PC1/3 availability, add a new element which must be considered in population and clinical studies of this gene.
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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.