Since the first administration of insulin to a person with diabetes in 1922, scientific contributions from academia and industry have improved insulin therapy and access. The pharmaceutical need for insulin is now more than 40 tons annually, half of which is produced by recombinant secretory expression in Saccharomyces cerevisiae. We discuss how, in this yeast species, adaptation of insulin precursors by removable structural elements is pivotal for efficient secretory expression. The technologies reviewed have been implemented at industrial scale and are seminal for the supply of human insulin and insulin analogues to people with diabetes now and in the future. Engineering of a target protein with removable structural elements may provide a general approach to yield optimisation.
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http://dx.doi.org/10.1016/j.tibtech.2023.09.012 | DOI Listing |
PLoS Negl Trop Dis
January 2025
Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
Background: The antigen Na-GST-1, expressed by the hookworm Necator americanus, plays crucial biochemical roles in parasite survival. This study explores the development of mRNA vaccine candidates based on Na-GST-1, building on the success of recombinant Na-GST-1 (rNa-GST-1) protein, currently assessed as a subunit vaccine candidate, which has shown promise in preclinical and clinical studies.
Methodology/findings: By leveraging the flexible design of RNA vaccines and protein intracellular trafficking signal sequences, we developed three variants of Na-GST-1 as native (cytosolic), secretory, and plasma membrane-anchored (PM) antigens.
J Histochem Cytochem
January 2025
Department of Veterinary Anatomy, College of Bioresource Sciences, Nihon University, Fujisawa, Japan.
SummaryPrevious studies have suggested that chromogranin A (CgA) is a partner molecule of secretogranin III (SgIII). In mouse pituitary corticotroph-derived AtT-20 cells, SgIII plays a role in sorting CgA/hormone aggregates into secretory granules (SGs). Although CgA expression is equivocal, CgB is clearly detectable in the rat pituitary corticotrophs.
View Article and Find Full Text PDFAging Cell
January 2025
Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Beijing, China.
The current mechanism by which aging reduces salivary secretion is unknown. This study investigates the mechanism of aging-related submandibular (SMG) dysfunction and evaluates the therapeutic potential of dental pulp stem cell-derived exosomes (DPSC-exos). We found that the stimulated salivary flow rate was significantly reduced in naturally aging and D-galactose-induced aging mice (D-gal mice) compared to control mice.
View Article and Find Full Text PDFBreast Cancer Res
January 2025
College of Pharmacy, Seoul National University, Seoul, 08826, South Korea.
Background: Patients with estrogen receptor (ER)-positive breast cancer (BC) can be treated with endocrine therapy targeting ER, however, metastatic recurrence occurs in 25% of the patients who have initially been treated. Secreted proteins from tumors play important roles in cancer metastasis but previous methods for isolating secretory proteins had limitations in identifying novel targets.
Methods: We applied an in situ secretory protein labeling technique using TurboID to analyze secretome from tamoxifen-resistant (TAMR) BC.
Int J Biol Sci
January 2025
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, China.
Skin fibrotic diseases are characterized by abnormal fibroblast function and excessive deposition of extracellular matrix. Our previous single-cell sequencing results identified an enriched fibroblast subcluster in skin fibrotic tissues that highly expresses the actin cross-linking cytoskeletal protein Transgelin (TAGLN), which bridges the mechanical environment of tissues and cellular metabolism. Therefore, we aimed to investigate the role of TAGLN in the pathogenesis of skin fibrosis.
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