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The catalytically inactive precursor of cathepsin D induces apoptosis in human fibroblasts and HeLa cells
Author(s) -
Schestkowa Olga,
Geisel Dominik,
Jacob Ralf,
Hasilik Andrej
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21269
Subject(s) - cathepsin d , pepstatin , hela , cathepsin , cathepsin s , cathepsin o , cathepsin l1 , cathepsin l , cytosol , cathepsin b , apoptosis , chemistry , microbiology and biotechnology , cathepsin a , enzyme , biochemistry , biology , cell , protease
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. J. Cell. Biochem. J. Cell. Biochem. 101: 1558–1566, 2007. © 2007 Wiley‐Liss, Inc.