Pleiotropic effects of cathepsin D.

Abstract

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.

• Authors: Aruna Vashishta, Sujata Saraswat Ohri, Vaclav Vetvicka
• Journal: Endocrine, metabolic & immune disorders drug targets (Endocr Metab Immune Disord Drug Targets) Vol. 9 Issue 4 Pg. 385-91 (Dec 2009) ISSN: 2212-3873 [Electronic] United Arab Emirates
• PMID: 19807669 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Cathepsin D

Topics

• Animals
• Apoptosis
• Cathepsin D (biosynthesis, genetics, physiology)
• Cell Proliferation
• Drug Design
• Humans
• Lysosomes (enzymology)
• Mice
• Neoplasm Metastasis
• Neoplasms (drug therapy, enzymology, pathology)
• Neuronal Ceroid-Lipofuscinoses (enzymology)
• Prognosis