Proteinolyse-unabhaengige proapoptotische Wirkung von Cathepsin D und Procathepsin D

Verschiedene Studien weisen auf eine Beteiligung von Cathepsin D an Apoptose hin. In manchen Systemen ist die durch Cathepsin D mediierte Apoptose durch seinen Inhibitor Pepstatin A hemmbar, in anderen ist die enzymatische Aktivität des Cathepsin D für seine apoptotische Involvierung entbehrlich. Di...

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Bibliographic Details
Main Author: Geisel, Olga
Contributors: Hasilik, Andrej (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2007
Online Access:PDF Full Text
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In several reports cathepsin D has been implicated in apoptosis. In some systems the effects of agents considered to be mediated by cathepsin D were inhibited in the presence of pepstatin A, an inhibitor of the enzyme. In other studies the effect of a mutant cathepsin D deprived of activity was indistinguishable from that of the normal enzyme. Here we show that in human fibroblasts and in HeLa cells apoptosis can be induced by microinjecting into cytosol either mature cathepsin D or its inactive precursor procathepsin D. The microinjected precursor remains in the uncleaved form. These results confirm that the proapoptotic effect of cathepsin D in the cytosol is independent of its catalytic activity and suggest that the interaction of cathepsin D with the downstream effector does not involve the active site of the enzyme, since in the proenzyme the active site is masked by the prosequence.