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- W2593983221 abstract "Cathepsin D (CTSD) is a member of the subfamily of lysosomalaspartic proteases. However, its enzymatic function is notrestricted solely to the acidic milieu of lysosomes. It canfacilitate cancer cell migration and invasion by digesting thebasement membrane, extracellular matrix, and connective tissue.Because of its mitogenic and proteolytic activities, CTSD hasbeen suggested to act as prognostic marker in many tumourtypes, especially breast cancer. CTSD has been also implicatedin positive and negative regulation of apoptosis. In this studywe investigated the role of CTSD in the TRAIL-induced apoptoticsignaling. TRAIL (Tumor necrosis factor -relatedapoptosis-inducing ligand) induces extrinsic apoptotic pathwayby binding to its plasma membrane death receptors.Interestingly, TRAIL induces apoptosis preferentially invarious types of tumor cells without significant toxicitytowards normal tissue. MDA-MB-231 breast carcinoma cells weretransfected with cDNA coding for CTSDwt and its enzymaticallyinactive counterpart (CTSDmut). Control and CTSDwt/CTSDmutoverexpressing stable transfectants were then exposed to TRAILand frequency of apoptosis was determined by nuclearfragmentation, PARP cleavage and activation of caspases. Inthis study we describe that CTSD facilitates the TRAIL-inducedapoptosis of breast cancer MDA-MB-231 cells in enzymaticactivity-dependent manner. Analysis of the potential substratesspecifically cleaved by CTSD during apoptotic cell deathprogression provided a new evidence of the CTSD-mediatedcleavage of the Bcl-2 protein. The Bcl-2 cleavage occurred bothin MDA-MB-231 cells and in vitro in a range of pH values asdetected by immunoblotting. As Bcl-2 is prominentanti-apoptotic regulator, its cleavage may represent novelmechanism of cathepsin D-mediated regulation of apoptosis." @default.
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- W2593983221 date "2014-06-23" @default.
- W2593983221 modified "2023-09-26" @default.
- W2593983221 title "Cleavage of Bcl-2 by cathepsin D: a novel mechanism ofcathepsin D-mediated regulation of apoptosis" @default.
- W2593983221 hasPublicationYear "2014" @default.
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