A precursor form of cathepsin B (Mr 45-47 kd) was purified from ascitic fluids of patients with ovarian adenocarcinomas. Following pepsin activation, this precursor produced a 33 kd cathepsin B-like proteinase closely related to lysosomal cathepsin B. A similar activation was found using the 52 kd pro-cathepsin D secreted by the MCF7 human breast cancer cells. This activation was a time, dose and pH dependent process. These results suggest that the 52 kd pro-cathepsin D may be involved in the early steps of the "metastatic cascade", activating pro-cathepsin B in an acidic environment.
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Biomed Pharmacother
December 2024
Calcium Cell Signaling Lab, IRBLleida, University of Lleida, Rovira Roure 80, Lleida 25198, Spain. Electronic address:
Diverse agents targeting (macro)autophagy, a critical metabolic stress response in cancer cells, have been proposed for cancer therapy. In previous studies, we showed that NNC-55-0396 (NNC) induces glioblastoma cell death by activating the Unfolded Protein Response (UPR) of ER stress and increasing cytosolic Ca levels. Here, we report that NNC affects both ends of the autophagy process, causing extensive cytoplasmic vacuolation.
View Article and Find Full Text PDFMol Genet Metab
October 2024
Department of Molecular Cell Biology and Medicine, Graduate School of Biomedical Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan. Electronic address:
We previously expressed a chimeric protein in which the small heat-shock protein αB-crystallin (αBC) is fused at its N-terminus to the C-terminus of the first transmembrane segment of the endoplasmic reticulum (ER) protein mitsugumin 23 and confirmed its localization to the ER. Moreover, overexpression of this N-terminally modified αBC was shown to prevent the aggregation of the coexpressed R120G αBC variant, which is highly aggregation-prone and associated with the hereditary myopathy αB-crystallinopathy. To uncover a molecular mechanism by which the ER-anchored αBC negatively regulates the protein aggregation, we isolated proteins that bind to the ER-anchored αBC and identified the lysosomal protease cathepsin D (CTSD) as one such interacting protein.
View Article and Find Full Text PDFCarbohydr Res
September 2024
Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, Gdansk, 80-308, Poland.
Cysteine cathepsins constitute the largest cathepsin family, with 11 proteases in human that are present primarily within acidic endosomal and lysosomal compartments. They are involved in the turnover of intracellular and extracellular proteins. They are synthesized as inactive procathepsins that are converted to mature active forms.
View Article and Find Full Text PDFCirc Res
March 2024
Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China (D.Z., Z.-K.H., Y.L., Z.-J.L., X.-W.Z., H.W., C.-S.L., X.S., M.-X.A., J.-X.S., Y.-H.C., W.-D.Z.).
Background: Microvascular complications are the major outcome of type 2 diabetes progression, and the underlying mechanism remains to be determined.
Methods: High-throughput RNA sequencing was performed using human monocyte samples from controls and diabetes. The transgenic mice expressing human CTSD (cathepsin D) in the monocytes was constructed using CD68 promoter.
Biol Chem
May 2024
Department of Biochemistry & Pharmacology, 2281 Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3052, Australia.
Proteases function within sophisticated networks. Altering the activity of one protease can have sweeping effects on other proteases, leading to changes in their activity, structure, specificity, localisation, stability, and expression. Using a suite of chemical tools, we investigated the impact of cathepsin X, a lysosomal cysteine protease, on the activity and expression of other cysteine proteases and their inhibitors in dendritic cells.
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