The ubiquitous enzymes peptidyl prolyl cis-trans isomerase (PPI, EC 5.2.1.8) and protein disulfide isomerase (PDI, EC 5.3.4.1) are important rate-limiting catalysts of protein-folding events in the cell. In the free-living nematode Caenorhabditis elegans, two genes encoding these enzymes (cyp-9 and pdi-1, respectively) are clustered together on chromosome III. In work described elsewhere, the encoded enzymes have been expressed as recombinant proteins and have been determined to possess in vitro PPI and PDI activity. Taken together, this organization of the two genes and the related functions of their transcripts indicate that they may be cotranscribed as a polycistronic unit, similar to bacterial operons. This study details the very close linkage of pdi-1 and cyp-9, which are in the same orientation. pdi-1 is the upstream gene, and the putative polyadenylation cleavage signal of this gene is separated from the trans-splice acceptor site of cyp-9 by only 103 bp. pdi-1 is trans-spliced by the ubiquitous nematode trans-spliced leader SL1, whereas cyp-9 was found to be predominantly trans-spliced by the "operon-specific" trans-spliced leader SL2. Similar trends in relative transcript abundance were demonstrated with synchronously produced mRNA for both genes during larval development, supporting the contention that the genes are co-expressed. Finally, reporter gene analysis provides strong evidence that both genes are controlled by a single upstream regulatory element, which directs expression of both enzymes in the hypodermal cells that synthesize the cuticle.
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http://dx.doi.org/10.1089/dna.1997.16.1335 | DOI Listing |
Tissue Cell
January 2025
Department of Biochemistry. All India Institute of Medical Sciences. Bhopal, Madhya Pradesh 462020, India. Electronic address:
Cells are susceptible to both oxidative and reductive stresses, with reductive stress being less studied and potentially therapeutic in cancer. Reductive stress, characterized by an excess of reducing equivalents exceeding the activity of endogenous oxidoreductases, can lead to an imbalance in homeostasis, causing an increase in reactive oxygen species induction, affecting cellular antioxidant load and flux. Unlike oxidative stress, reductive stress has been understudied and poorly understood, and there is still much to learn about its mechanisms in cancer, its therapeutic potential, and how cancer cells react to it.
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Vet Products Research & Innovation Center Co., Ltd, 141 Moo9, Thailand Science Park, Innovation Clusters (INC2) Tower D 11th floor, Room No. INCD1108-INCD1111 Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathum Thani, 12120, Thailand.
Recently, microsporidiosis caused by a microsporidian [Ecytonucleospora (Enterocytozoon) hepatopenaei, EHP] has been found to seriously impact the global shrimp industry. The aim of this study was to evaluate the therapeutic effects of fumaric acid (FA) in EHP-infected Pacific white shrimp (Penaeus vannamei). In the first 2 groups, non-EHP-infected shrimp were fed FA-supplemented (10 g/kg diet) or normal feed (CM+ and CM-, respectively).
View Article and Find Full Text PDFCell Rep Med
January 2025
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA. Electronic address:
Alpha-1 antitrypsin (AAT) deficiency (AATD) is a monogenic disease caused by misfolding of AAT variants resulting in gain-of-toxic aggregation in the liver and loss of monomer activity in the lung leading to chronic obstructive pulmonary disease (COPD). Using high-throughput screening, we discovered a bioactive natural product, phenethyl isothiocyanate (PEITC), highly enriched in cruciferous vegetables, including watercress and broccoli, which improves the level of monomer secretion and neutrophil elastase (NE) inhibitory activity of AAT-Z through the endoplasmic reticulum (ER) redox sensor protein disulfide isomerase (PDI) A4 (PDIA4). The intracellular polymer burden of AAT-Z can be managed by combination treatment of PEITC and an autophagy activator.
View Article and Find Full Text PDFJ Thromb Haemost
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Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA. Electronic address:
Biochim Biophys Acta Mol Basis Dis
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Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:
Cole-Carpenter syndrome (CCS) is a rare autosomal-dominant genetic disease characterized by craniosynostosis, ocular proptosis, hydrocephalus, distinctive facial features, and bone fragility. Previous cases of CCS are associated with genetic variations in P4HB, which encodes the protein disulfide isomerase (PDI), a key enzyme in protein folding. Patients with CCS caused by P4HB mutations often present with short stature, limb deformities, and abnormal epiphyseal plates.
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