Pleiotropic effects of cathepsin D.
Over the past decades, the paradigm that lysosomal enzymes participate only in non-specific protein degradation during cell death has changed. Studies conducted both in cell cultures and in animals defined the role of these enzymes that includes cathepsin D (CD). Knockout mice revealed the role of CD in postnatal tissue homeostasis and remodeling. Mutations that abolish the CD enzymatic activity have been implicated in neural ceroid lipofuscinosis. Recent studies suggested a differential role of CD in regulation of apoptosis. The zymogen of CD, procathepsin D (pCD), is secreted by various cancer cells. Extensive studies showed that it acts as a mitogen on both cancer and stromal cells by stimulating their invasive and metastatic properties. Additional studies suggested that procathepsin D/CD is an independent prognostic factor in various cancers, leading to the investigations of pCD/CD as a potential target for designing anti-cancer therapy. In this review, we described the various forms of CD and their implications in numerous physiological as well as pathological conditions.
Vashishta
Aruna
A
Department of Pathology, School of Medicine, University of Louisville, Louisville, KY 40202, USA.
Ohri
Sujata Saraswat
SS
Vetvicka
Vaclav
V
D000818:Animals; D017209:Apoptosis; D002402:Cathepsin D / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D015195:Drug Design; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D051379:Mice; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D009472:Neuronal Ceroid-Lipofuscinoses / Q000201:enzymology; D011379:Prognosis
D002402:Cathepsin D