ArticleThe Journal of cell biology2001
Intracellular retention of newly synthesized insulin in yeast is caused by endoproteolytic processing in the Golgi complex.
Article in The Journal of cell biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 86 citations in OpenAlex.
- VPS13D Gene Variant Is Associated with Altered IL-6 Production and Mortality in Septic Shock.Journal of innate immunity · 2015Trial
- Engineering Saccharomyces cerevisiae secretory system for recombinant protein production: strategies from signal peptides to protease control.Archives of microbiology · 2026Review
- EngineeringEngineering microbiology · 2024Review
- Genome-wide screen identifies new set of genes for improved heterologous laccase expression in Saccharomyces cerevisiae.Microbial cell factories · 2024Article
- Engineering strategies for enhanced heterologous protein production by Saccharomyces cerevisiae.Microbial cell factories · 2024Review
- Improving therapeutic protein secretion in the probiotic yeast Saccharomyces boulardii using a multifactorial engineering approach.Microbial cell factories · 2023Article
- The Regulated Secretion and Models of Intracellular Transport: The Goblet Cell as an Example.International journal of molecular sciences · 2023Review
- Alleviating vacuolar transport improves cellulase production in Trichoderma reesei.Applied microbiology and biotechnology · 2023Article
- Customized yeast cell factories for biopharmaceuticals: from cell engineering to process scale up.Microbial cell factories · 2021Review
- Mining Data From Plasma Cell Differentiation Identified Novel Genes for Engineering of a Yeast Antibody Factory.Frontiers in bioengineering and biotechnology · 2020Article
- RNAi expression tuning, microfluidic screening, and genome recombineering for improved protein production inProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Vacuolar Protein Sorting 4B (VPS4B) Regulates Apoptosis of Chondrocytes via p38 Mitogen-Activated Protein Kinases (MAPK) in Osteoarthritis.Inflammation · 2017Article
- Systematic Optimization of Protein Secretory Pathways inFrontiers in microbiology · 2017Article
- Changes in the expression of the type 2 diabetes-associated gene VPS13C in the β-cell are associated with glucose intolerance in humans and mice.American journal of physiology. Endocrinology and metabolism · 2016Article
- High CHMP4B expression is associated with accelerated cell proliferation and resistance to doxorubicin in hepatocellular carcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- [Analysis of differentially expressed proteome in urine from non-small cell lung cancer patients].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2015Article
- Gene expression profiling for human iPS-derived motor neurons from sporadic ALS patients reveals a strong association between mitochondrial functions and neurodegeneration.Frontiers in cellular neuroscience · 2015Article
- Vacuolar protein sorting 4B, an ATPase protein positively regulates the progression of NSCLC via promoting cell division.Molecular and cellular biochemistry · 2013Article
- Current state and recent advances in biopharmaceutical production in Escherichia coli, yeasts and mammalian cells.Journal of industrial microbiology & biotechnology · 2013Review
- Different expression systems for production of recombinant proteins in Saccharomyces cerevisiae.Biotechnology and bioengineering · 2012Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
An insulin-containing fusion protein (ICFP, encoding the yeast prepro-alpha factor leader peptide fused via a lysine-arginine cleavage site to a single chain insulin) has been expressed in Saccharomyces cerevisiae where it is inefficiently secreted. Single gene disruptions have been identified that cause enhanced immunoreactive insulin secretion (eis). Five out of six eis mutants prove to be vacuolar protein sorting (vps)8, vps35, vps13, vps4, and vps36, which affect Golgi<-->endosome trafficking. Indeed, in wild-type yeast insulin is ultimately delivered to the vacuole, whereas vps mutants secrete primarily unprocessed ICFP. Disruption of KEX2, which blocks intracellular processing to insulin, quantitatively reroutes ICFP to the cell surface, whereas loss of the Vps10p sorting receptor is without effect. Secretion of unprocessed ICFP is not based on a dominant secretion signal in the alpha-leader peptide. Although insulin sorting mediated by Kex2p is saturable, Kex2p functions not as a sorting receptor but as a protease: replacement of Kex2p by truncated secretory Kex2p (which travels from Golgi to cell surface) still causes endoproteolytic processing and intracellular insulin retention. Endoproteolysis promotes a change in insulin's biophysical properties. B5His residues normally participate in multimeric insulin packing; a point mutation at this position permits ICFP processing but causes the majority of processed insulin to be secreted. The data argue that multimeric assembly consequent to endoproteolytic maturation regulates insulin sorting in the secretory pathway.
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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.