ArticleThe Journal of clinical investigation2013
Dominant protein interactions that influence the pathogenesis of conformational diseases.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
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.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Structural Communication Between C-Peptide and Insulin Within the Proinsulin Molecule.International journal of molecular sciences · 2026Article
- Defective Thyroglobulin: Cell Biology of Disease.International journal of molecular sciences · 2022Review
- Distinct states of proinsulin misfolding in MIDY.Cellular and molecular life sciences : CMLS · 2021Article
- Normal and defective pathways in biogenesis and maintenance of the insulin storage pool.The Journal of clinical investigation · 2021Review
- Lessons from animal models of endocrine disorders caused by defects of protein folding in the secretory pathway.Molecular and cellular endocrinology · 2020Review
- Misfolded proinsulin impairs processing of precursor of insulin receptor and insulin signaling in β cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Defective endoplasmic reticulum export causes proinsulin misfolding in pancreatic β cells.Molecular and cellular endocrinology · 2019Article
- Misfolded proinsulin in the endoplasmic reticulum during development of beta cell failure in diabetes.Annals of the New York Academy of Sciences · 2018Review
- Hypothalamic ER-associated degradation regulates POMC maturation, feeding, and age-associated obesity.The Journal of clinical investigation · 2018Article
- Autophagy is a major regulator of beta cell insulin homeostasis.Diabetologia · 2016Article
- Hyperglucagonemia in an animal model of insulin- deficient diabetes: what therapy can improve it?Clinical diabetes and endocrinology · 2016Article
- Disruption of O-linked N-Acetylglucosamine Signaling Induces ER Stress and β Cell Failure.Cell reports · 2015Article
- Revisiting PC1/3 Mutants: Dominant-Negative Effect of Endoplasmic Reticulum-Retained Mutants.Endocrinology · 2015Article
- Proinsulin misfolding and endoplasmic reticulum stress during the development and progression of diabetes.Molecular aspects of medicine · 2015Review
- INS-gene mutations: from genetics and beta cell biology to clinical disease.Molecular aspects of medicine · 2015Review
- Defective transport of the obesity mutant PC1/3 N222D contributes to loss of function.Endocrinology · 2014Article
- Surveying the floodgates: estimating protein flux into the endoplasmic reticulum lumen in Saccharomyces cerevisiae.Frontiers in physiology · 2014Article
- Endoplasmic reticulum oxidoreductin-1α (Ero1α) improves folding and secretion of mutant proinsulin and limits mutant proinsulin-induced endoplasmic reticulum stress.The Journal of biological chemistry · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Misfolding of exportable proteins can trigger endocrinopathies. For example, misfolding of insulin can result in autosomal dominant mutant INS gene-induced diabetes of youth, and misfolding of thyroglobulin can result in autosomal recessive congenital hypothyroidism with deficient thyroglobulin. Both proinsulin and thyroglobulin normally form homodimers; the mutant versions of both proteins misfold in the ER, triggering ER stress, and, in both cases, heterozygosity creates potential for cross-dimerization between mutant and WT gene products. Here, we investigated these two ER-retained mutant secretory proteins and the selectivity of their interactions with their respective WT counterparts. In both cases and in animal models of these diseases, we found that conditions favoring an increased stoichiometry of mutant gene product dominantly inhibited export of the WT partner, while increased relative level of the WT gene product helped to rescue secretion of the mutant partner. Surprisingly, the bidirectional consequences of secretory blockade and rescue occur simultaneously in the same cells. Thus, in the context of heterozygosity, expression level and stability of WT subunits may be a critical factor influencing the effect of protein misfolding on clinical phenotype. These results offer new insight into dominant as well as recessive inheritance of conformational diseases and offer opportunities for the development of new therapies.
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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.