Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human plasma fibronectin (pFN) contains a cryptic metalloprotease present in the collagen-binding domain. The enzyme could be generated and activated in the presence of Ca2+ from the purified 70-kDa pFN fragment produced by cathepsin D digestion. In this work we cloned and expressed the metalloprotease, designated FN type IV collagenase (FnColA), and a truncated variant (FnColB) in E. coli. The recombinant pFN protein fragment was isolated from inclusion bodies, and subjected to folding and autocatalytic degradation in the presence of Ca2+, and yielded an active enzyme capable of digesting gelatin, helical type II and type IV collagen, alpha- and beta-casein, insulin b-chain, and a synthetic Mca-peptide. In contrast, isolated plasma fibronectin, type I collagen, and the DNP-peptide were no substrates. Both catalytically active recombinant pFN fragments were efficiently inhibited by EDTA, and batimastat, and, in contrast to the glycosylated enzyme isolated from plasma fibronectin, were also inhibited by TIMP-2.
 ...
PMID:The proteolytic activity of the recombinant cryptic human fibronectin type IV collagenase from E. coli expression. 1130 53

CT120, a novel membrane-associated gene implicated in lung carcinogenesis, was previously identified from chromosome 17p13.3 locus, a hot mutation spot involved in human malignancies. In the present study, we further determined that CT120 ectopic expression could promote cell proliferation activity of NIH3T3 cells using MTS assay, and monitored the downstream effects of CT120 in NIH3T3 cells with Atlas mouse cDNA expression arrays. Among 588 known genes, 133 genes were found to be upregulated or downregulated by CT120. Two major signaling pathways involved in cell proliferation, cell survival and anti-apoptosis were overexpressed and activated in response to CT120: One is the Raf/MEK/Erk signal cascades and the other is the PI3K/Akt signal cascades, suggesting that CT120 might contribute, at least in part, to the constitutively activation of Erk and Akt in human lung cancer cells. In addition, some tumor metastasis associated genes cathepsin B, cathepsin D, cathepsin L, MMP-2/TIMP-2 were also upregulated by CT120, upon which CT120 might be involved in tumor invasiveness and metastasis. In addition, CT120 might play an important role in tumor progression through modulating the expression of some candidate "Lung Tumor Progression" genes including B-Raf, Rab-2, BAX, BAG-1, YB-1, and Cdc42.
 ...
PMID:Altered gene expression profiles of NIH3T3 cells regulated by human lung cancer associated gene CT120. 1562 16

Epithelial ovarian cancer cells spread by two major pathways. One is by exfoliation of tumor cells from the ovarian surface, with resulting implants on peritoneal surfaces such as omentum, diaphragm, and bowel serosa. The second pathway of spread of epithelial ovarian cancer is that of invasion into lymphatic channels, with involvement of the retroperitoneal lymph nodes. Invasion of tumor cells appears to result from a deregulation of the normal processes that govern physiologic controlled invasion. An example of physiologic invasion is that of trophoblastic implantation of the endometrium followed by invasion to access the maternal blood supply in the uterus. The normal invasive process is controled by a balance between protease activity and that of their inhibitors at the level of the individual cell. For the large majority of tumors, extracellular matrix degrading proteases have been shown to have an important role in tumor invasion and metastases. In epithelial ovarian cancer, the major focus has been on the activities of the serine protease urokinase plasminogen activator (uPA) (1-4), and the matrix metalloproteinases (MMP) (5,6). The cysteine proteases, such as cathepsin B, and aspartic proteases, such as cathepsin D, also play a role in invasive-ness of ovarian cancer cells. Each class of proteases contributes to the process of invasion, and cooperates with each other to further the optimal degradation of the extracellular matrix by ovarian cancer cells (7). Urokinase activates plasminogen to plasmin, which activates both pro-uPA and latent MMPs, and cleaves the MMP inhibitor TIMP-2. Moreover, cathepsin B, which is expressed by ovarian cancer cells, appears to facilitate the action of uPA, most likely by activating pro-uPA (8).
 ...
PMID:In vitro invasion assays. 2134 Jul 70