Disease relevance of Ctsc

• Mutation analysis of the cathepsin C gene in Indian families with Papillon-Lefèvre syndrome [1].
• After 6 or 12 weeks of hypertension, specific activities of all enzymes measured were significantly increased, levels ranging from 24% above normal for cathepsin C to 351% above normal for N-acetyl-beta-glucosaminidase [2].
• Apparently, cathepsin C is transferred in Morris hepatoma 7777 cells by a mechanism independent of mannose-6-phosphate-specific receptors [3].
• In freshly isolated hepatocytes cathepsin C was processed to forms closely related to those found in the hepatoma cells [3].

High impact information on Ctsc

• The molecular forms of two lysosomal enzymes, cathepsin C and cathepsin D, have been examined in lysosomes and coated vesicles (CVs) of rat liver [4].
• Molecular cloning of cDNA for rat cathepsin C. Cathepsin C, a cysteine proteinase with an extremely long propeptide [5].
• The deduced amino acid sequence of cathepsin C comprises 462 amino acid residues: 28 NH2-terminal residues corresponding to the signal peptide, 201 residues corresponding to the propeptide, and 233 COOH-terminal residues corresponding to the mature enzyme region [5].
• Isolated hepatocytes were incubated with vinblastine to induce autophagosome accumulation; the cells were then homogenized and treated with the cathepsin C substrate glycyl-l-phenylalanine 2-naphthylamide to cause osmotic disruption of the lysosomes [6].
• Use of glycyl-L-phenylalanine 2-naphthylamide, a lysosome-disrupting cathepsin C substrate, to distinguish between lysosomes and prelysosomal endocytic vacuoles [7].

Biological context of Ctsc

• Our results show that at least one of the three glycosylation sites in the propeptide must be glycosylated in order to obtain targeting and maturation of cathepsin C [8].
• The primary structure and tissue distribution of cathepsin C [9].
• The reactivity of endoglycosidase H and N-glycanase and analysis of phosphorylation indicated that both precursor and mature cathepsin C are phosphorylated and N-glycosylated to give a high-mannose-type [10].
• We present evidence that the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) is a site for protein splicing of cathepsin C: (i) maturation of the enzyme in COS 7 cells is a two-step process starting within the ERGIC, and (ii) the intermediately processed polypeptide retains both termini of the proenzyme and lacks an internal fragment [11].

Anatomical context of Ctsc

• Active cathepsin C is found in lysosomes as a 200-kDa multimeric enzyme [8].
• By double immunostaining using confocal laser microscopy, immunoreactivity for cathepsin H was found to be co-localized with that for cathepsin C or TPP-I in both type II cells and macrophages [12].
• Immunohisto/cytochemical observations demonstrated that positive staining for cathepsin C and TPP-I was more intensely localized in alveolar epithelial regions than in bronchial or bronchiolar epithelial cells [12].
• Fluorescence demonstration of dipeptidyl peptidase I (cathepsin C) in skeletal, cardiac, and vascular smooth muscles [13].
• A combination of pulse-chase experiments and the subcellular fractionation analysis showed that procathepsin C and cathepsin C are located in low-buoyant-density organelles and lysosomes, respectively [10].

Associations of Ctsc with chemical compounds

• Cathepsin C, therefore, is a member of the papain family, although its propeptide region is much longer than those of other cysteine proteinases and shows no significant amino acid sequence similarity to any other cysteine proteinase [5].
• In order to assess some aspects of this contribution, we transiently expressed mutant molecules of rat cathepsin C either lacking three of the four glycosylation sites, partially deleted in the proregion, or mutated at tryptophan 39 also located in the proregion, and studied their biosynthesis [8].
• Cathepsin C activity is reduced when thioethylamine hydrochloride is omitted from the incubation medium [14].
• 1 mM-ZnSO4 considerably inhibits the cathepsin C total activity, measured with Gly-L-Phe-2-NNap as the substrate, in the presence of Triton X-100 [14].
• Dipeptidyl peptidase I (DPPI, cathepsin C) is a lysosomal cysteine protease that can activate zymogens of several different serine proteases by one step or sequential removal of dipeptides from the N-termini of the pro-protease protein substrates [15].

Other interactions of Ctsc

• It was separated from cathepsin J using a Sephacryl S-200 gel-filtration column and was further separated from cathepsin H by DEAE-Sephadex A-50 anion-exchange column chromatography [16].
• The present immunohistochemical study further examined the localization of lysosomal aminopeptidases, cathepsin C, and tripeptidyl peptidase I (TPP-I) in the rat lung [12].
• Subpopulations of CVs prepared by either procedure showed similar results, when examined for their relative proportion of cathepsin C and cathepsin D precursors [4].

Analytical, diagnostic and therapeutic context of Ctsc

• Western blotting confirmed the presence of cathepsin C and TPP-I as active forms in the pulmonary tissue, showing 25 kD and 47 kD, respectively [12].
• Immunoelectron microscopy revealed the gold labeling of cathepsin C or TPP-I in multivesicular and composite bodies, and lamellar bodies of Type II cells [12].
• Distribution of radioactivity was established after differential and isopycnic centrifugation and compared with that of cathepsin C, a lysosomal enzyme [17].
• The synthesis, transport and processing of cathepsin C was studied in Morris hepatoma 7777 cells by metabolic labelling, immunoprecipitation and characterization of labelled polypeptides by gel electrophoresis and fluorography [3].

References