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@article{759950, author = {Beneš, Petr and Větvička, Václav and Fusek, Martin}, article_number = {1}, keywords = {Alzheimer disease; Apoptosis; Atherosclerosis; Aspartic protease; Cancer; Cathepsin D; Knock-out mice; Procathepsin D}, language = {eng}, issn = {1040-8428}, journal = {Critical Reviews in Oncology/Hematology}, title = {CATHEPSIN D : MANY FUNCTIONS OF ONE ASPARTIC PROTEASE}, volume = {68}, year = {2008} }
TY - JOUR ID - 759950 AU - Beneš, Petr - Větvička, Václav - Fusek, Martin PY - 2008 TI - CATHEPSIN D : MANY FUNCTIONS OF ONE ASPARTIC PROTEASE JF - Critical Reviews in Oncology/Hematology VL - 68 IS - 1 SP - 12-28 EP - 12-28 PB - ELSEVIER SN - 10408428 KW - Alzheimer disease KW - Apoptosis KW - Atherosclerosis KW - Aspartic protease KW - Cancer KW - Cathepsin D KW - Knock-out mice KW - Procathepsin D N2 - For years, it has been held that cathepsin D (CD) is involved in rather non-specific protein degradation in a strongly acidic milieu of lysosomes. Studies with CD knock-out mice revealed that CD is not necessary for embryonal development, but it is indispensable for postnatal tissue homeostasis. Mutation that abolishes CD enzymatic activity causes neuronal ceroid lipofuscinosis (NCL) characterized by severe neurodegeneration, developmental regression, visual loss and epilepsy in both animals and humans. In the last decade, however, an increasing number of studies demonstrated that enzymatic function of CD is not restricted solely to acidic milieu of lysosomes with important consequences in regulation of apoptosis. In addition to CD enzymatic activity, it has been shown that apoptosis is also regulated by catalytically inactive mutants of CD which suggests that CD interacts with other important molecules and influences cell signaling. Moreover, procathepsin D (pCD), secreted from cancer cells, acts as a mitogen on both cancer and stromal cells and stimulates their pro-invasive and pro-metastatic properties. Numerous studies found that pCD/CD level represents an independent prognostic factor in a variety of cancers and is therefore considered to be a potential target of anti-cancer therapy. Studies dealing with functions of cathepsin D are complicated by the fact that there are several simultaneous forms of CD in a cell-pCD, intermediate enzymatically active CD and mature heavy and light chain CD. It became evident that these forms may differently regulate the above-mentioned processes. In this article, we review the possible functions of CD and its various forms in cells and organisms during physiological and pathological conditions. ER -
BENEŠ, Petr, Václav VĚTVIČKA and Martin FUSEK. CATHEPSIN D : MANY FUNCTIONS OF ONE ASPARTIC PROTEASE. \textit{Critical Reviews in Oncology/Hematology}. ELSEVIER, 2008, vol.~68, No~1, p.~12-28. ISSN~1040-8428.
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