Disease relevance of CTSZ

• Using antibodies raised against recombinant cathepsin P produced in Escherichia coli, a single protein band of 33 kDa was detected by immunoblotting an extract of human liver [1].
• Cathepsin X was also up-regulated in gastric cancer (3-12-fold) compared to non-neoplastic mucosa [2].
• Patients with H. pylori gastritis showed significantly higher cathepsin X mRNA (2.5-fold) and protein (1.6-fold) expression than H. pylori-negative patients [2].
• Up-regulation of cathepsin X in Helicobacter pylori gastritis and gastric cancer [2].
• Up-regulation of cathepsin X in prostate cancer and prostatic intraepithelial neoplasia [3].

High impact information on CTSZ

• Here we show that a cathepsin-Z-related glycoprotein binds to the recycling, mannose-specific membrane lectin ERGIC-53 [4].
• Mutation of the lectin domain of ERGIC-53 selectively decreased YFP complementation with cathepsin Z [5].
• The integrin-binding motifs RGD and ECD, present in the pro- and in mature forms of cathepsin X, respectively, suggest that this enzyme might have a function in cell signaling and adhesion [6].
• Our results indicate that active cathepsin X mediates the function of beta(2) integrin receptors during cell adhesion and that it could also be involved in other processes associated with beta(2) integrin receptors such as phagocytosis and T cell activation [6].
• Using confocal microscopy, we demonstrated that the pro-form of cathepsin X was co-localized with beta(2) and beta(3) integrin subunits and its mature form solely with the beta(2) integrin subunit with the most intense signal in cell-cell junctions in differentiated U-937 cells and in co-cultures with endothelial cells [6].

Chemical compound and disease context of CTSZ

• We targeted two specific gene products, the O. volvulus cathepsin L (Ov-CPL) and cathepsin Z-like (Ov-CPZ) cysteine proteases, which were proposed to function during O. volvulus L3 molting [7].

Biological context of CTSZ

• Characterization of TH1 and CTSZ, two non-imprinted genes downstream of GNAS1 in chromosome 20q13 [8].
• The cathepsin X cDNA is ubiquitously expressed in human tissues and contains an open reading frame of 912 nucleotides encoding a predicted protein of 303 amino acids [9].
• A novel cDNA encoding a cysteine protease of the papain family named cathepsin X was obtained by PCR amplification from a human ovary cDNA library [9].
• Defining the substrate specificity of mouse cathepsin P [10].
• The most pronounced feature of the cathepsin X structure is the mini-loop that includes a short three-residue insertion protruding into the active site of the protease [11].

Anatomical context of CTSZ

• A polymorphism was again identified within the CTSZ 3' untranslated region and used to demonstrate biallelic expression in fetal tissues [8].
• Acidification of cells inhibited the association of ERGIC-53 with the known cargo cathepsin Z-related protein and dissociation of this glycoprotein in the ERGIC was impaired by organelle neutralization that did not impair the transport of a control protein [12].
• Recently, we identified increased cathepsin X expression in H. pylori-infected gastric mucosa [2].
• Cathepsin X was predominantly expressed by macrophages in the mucosal stroma and in glands of the antral mucosa [2].
• In vitro cell culture experiments revealed that intercellular signalling between pathogenicity island (PAI)-positive H. pylori-infected epithelial cells and macrophages via soluble factors in the culture medium seems to be responsible for increased expression of cathepsin X in monocytes [2].

Associations of CTSZ with chemical compounds

• Human cathepsin X: a novel cysteine protease of the papain family with a very short proregion and unique insertions [9].
• Cathepsin X also cleaved substrates with amide-blocked C-terminal carboxyl group with rates similar to those of the unblocked substrates [13].

Physical interactions of CTSZ

• CONCLUSIONS: The structure of cathepsin X exhibits a binding surface that will assist in the design of specific inhibitors of cathepsin X as well as of cathepsin B and thereby help to clarify the physiological roles of both proteases [11].
• ERGIC-53 also interacts with the two lysosomal glycoproteins cathepsin Z and cathepsin C [14].

Other interactions of CTSZ

• Cathepsin X was similar to cathepsin B and found to be a carboxypeptidase with preference for a positively charged Arg in P1 position [13].

Analytical, diagnostic and therapeutic context of CTSZ

• Identification and molecular cloning of cathepsin P, a novel human putative cysteine protease of the papain family [15].
• Cathepsin X was detected in gastric mucosa by quantitative real-time RT-PCR, western blotting and immunohistochemistry [2].
• Induction of cathepsin X expression in epithelial and inflammatory cells caused by H. pylori infection was tested in in vitro contact and non-contact co-cultures of AGS cells and monocytic cells [2].
• Using quenched fluorogenic substrates and HPLC measurements, it was shown that cathepsin X preferentially cleaves substrates through a monopeptidyl carboxypeptidase pathway, while cathepsin B displays a preference for the dipeptidyl pathway [16].
• Cathepsin X was quantified at both protein and mRNA levels using several detection methods: Western blotting, immunohistochemistry, quantitative RT-PCR, and in situ hybridization [3].

References