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malfunction
in CHO cells deficient of S1P (termed SRD-12B cells) glycoprotein GP-C processing is abrogated after Lassa virus infection
malfunction
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postnatal ablation of site-1 protease results in chondrodysplasia and rapid growth plate disruption due to intracellular Col II entrapment concomitant with loss of chondrocyte hypertrophy. S1P ablation at E10.5 results in a complete loss of endochondral bone formation along with the presence of an enhanced cortical bone formation
malfunction
enzyme SKI-1 inhibition induces apoptosis of melanoma cells by a non-ATF6-dependent mechanism, overview
malfunction
soluble enzyme is unable to process arenavirus glycoproteinss at the cell surface
physiological function
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site-1 protease has fundamental roles in the preservation of postnatal growth plate through chondrocyte differentiation and Col II deposition and functions to couple growth plate maturation to trabecular bone development in growing mice
physiological function
a crucial step in the life cycle of arenaviruses is the biosynthesis of the mature fusion-active viral envelope glycoprotein that is essential for virus-host cell attachment and entry. The maturation of the arenavirus envelope glycoprotein precursor critically depends on proteolytic processing by the cellular proprotein convertase subtilisin kexin isozyme-1/site-1 protease
physiological function
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the Arabidopsis membrane-associated transcription factor, bZIP28, is the functional equivalent of mammalian ATF6, which relocates from the endoplasmic reticulum to the Golgi where it is proteolytically processed by the enzyme and released from the membrane to the nucleus to mediate the unfolded protein response to either promote cell survival or programmed cell death depending on different developmental context or stress severity. The canonical site-1 protease cleavage site plays a pivotal role in activation and function of bZIP28 during unfolded protein response in plants
physiological function
the arenaviruses are an important family of emerging viruses that includes several causative agents of severe hemorrhagic fevers in humans that represent serious public health problems. A crucial step of the arenavirus life cycle is maturation of the envelope glycoprotein precursor by the cellular subtilisin kexin isozyme 1/site 1 protease
physiological function
the enzyme plays crucial roles in cellular homeostatic functions and is hijacked by pathogenic viruses for the processing of their envelope glycoproteins. Zymogen activation of the enzyme involves sequential autocatalytic processing of its N-terminal prodomain at sites B'/B followed by the C'/C sites. All incompletely matured intermediates of SKI-1/S1P showed full catalytic activity toward cellular substrates, whereas optimal cleavage of viral glycoproteins depended on B'/B processing. Incompletely matured forms of SKI-1/S1P further process cellular and viral substrates in distinct subcellular compartments
physiological function
the enzyme regulates cartilage development, bone mineralization, and processing of viral glycoproteins, its overexpression is linked to carcinogenesis in some solid tumors, biological role of enzyme SKI-1 in melanoma development, overview
physiological function
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S1P ablation in the osterix lineage results in osteochondrodysplasia and variable degrees of early postnatal scoliosis. Embryonically, Runx2 and osterix expression are normal, but S1P ablation results in a delay in vascular invasion and endochondral bone development. Mice appear normal when born, but by day 7 display pronounced dwarfism with fragile bones that exhibit significantly reduced mineral density, mineral apposition rate, bone formation rate and reduced osteoblasts. Mice suffer from a drastic reduction in bone marrow mesenchymal progenitors and a drastic reduction in hematopoietic lineage-negative, endothelial-negative, CD105+ skeletal stem cells. Bone marrow mesenchymal progenitors are unable to differentiate into osteoblasts in vitro, with no effect on adipogenic differentiation
physiological function
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inhibition of S1P enzymatic activity in human hepatoma Huh-7.5.1 cells results in a robust reduction of the numbers of lipid droplets and lipid droplet-positive areas and effectively inhibits infection by dengue virsu DENV. Pre-treatment of Huh-7.5.1 cells with PF-429242 results in a dose-dependent inhibition of DENV and an about 3-log decrease in DENV-2 titer with 20 microM of PF-429242. Post-treatment of DENV-2 infected Huh-7.5.1 cells with PF-429242 does not affect viral RNA abundance, but it does compromise the assembly and/or release of infectious virus particles. PF-429242 antiviral activity is reversed by exogenous oleic acid
physiological function
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inhibition of site-1 protease leads to a profound reduction in plasmablast number linked to induction of autophagy. Plasmablasts generated in the presence of site-1 protease inhibitor segregate into CD38high and CD38low populations, the latter characterized by a marked reduction in the capacity to secrete IgG. Site-1 protease inhibition is accompanied by a distinctive change in gene expression associated with amino acid, steroid and fatty acid synthesis pathways
physiological function
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siRNA-mediated reduction of endogenous S1P in cChinese hamster ovary cells attenuates soluble (pro)renin receptor generation. Overexpression of S1P by transient transfection in this cell line increases s(P)RR generation. The S1P inhibitor PF429242 suppresses the generation of soluble (pro)renin receptor
additional information
9 amino acid residues at the cleavage site (P1-P8) and P1' are necessary and sufficient to define the subcellular location of processing and to determine to what extent processing of a substrate depends on SKI-1/S1P maturation
additional information
modeling of the SKI-1/S1P catalytic pocket identifies Y285 as a residue that potentially interacts with arenavirus envelope glycoprotein precursor residue Y253. The the catalytic triad is formed by residues D218, H249, and S414
additional information
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modeling of the SKI-1/S1P catalytic pocket identifies Y285 as a residue that potentially interacts with arenavirus envelope glycoprotein precursor residue Y253. The the catalytic triad is formed by residues D218, H249, and S414
additional information
the transmembrane anchorage and the cytoplasmic domain of SKI-1/S1P are dispensable for arenavirus glycoprotein processing