Two Faces of Cathepsin D: Physiological Guardian Angel and Pathological Demon
Zhila Khalkhali-Ellis* and Mary J.C. Hendrix
Stanley Manne Children’s Research Institute, †Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 2300 Children’s Plaza, Box 222, Chicago, Illinois, 60614-3394, USA.
- Corresponding Author:
- Zhila Khalkhali-Ellis
Stanley Manne Children’s Research Institute
225 East Chicago Ave., Box 222,Chicago, Illinois, 60614-3394, USA
E-mail: [email protected]
Received May 14, 2014; Accepted July 20, 2014; Published July 27, 2014
Citation: Zhila Khalkhali-Ellis and Mary J.C. Hendrix (2014) Two Faces of Cathepsin D: Physiological Guardian Angel and Pathological Demon. Biol Med 6:206. doi:10.4172/0974-8369.1000206
Copyright: © 2014 Ellis, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Since its discovery as a lysosomal hydrolase, Cathepsin D (CatD) has been the subject of intensive scrutiny by numerous scientists. Those accumulated efforts have defined its biosynthetic pathway, structure, and companion proteins in the context of its perceived “house keeping” function. However, in the past two decades CatD has emerged as a multifunctional enzyme, involved in myriad biological processes beyond its original “housekeeping” role. CatD is responsible for selective and limited cleavage (quite distinct from non-specific protein degradation) of particular substrates vital to proper cellular function. These proteolytic events are critical in the control of biological processes, including cell cycle progression, differentiation and migration, morphogenesis and tissue remodeling, immunological processes, ovulation, fertilization, neuronal outgrowth, angiogenesis, and apoptosis. Consistent with the biological relevance of CatD, its deficiency, altered regulation or post-translational modification underlie important pathological conditions such as cancer, atherosclerosis, neurological and skin disorders. Specifically, deregulated synthesis, post-translational modifications and hyper-secretion of CatD, along with its mitogenic effects, are established hallmarks of cancer. More importantly, but less studied, is its significance in regulating the sensitivity to anticancer drugs. This review outlines CatD’s post-translational modifications, cellular trafficking, secretion and protein binding partners in normal mammary gland, and restates the “site-specific” function of CatD which is most probably dictated by its post-translational modifications and binding partners. Noteworthy, CatD’s association with one of its binding partners in the context of drug sensitivity is highlighted, with the optimism that it could contribute to the development of more effective chemotherapeutic agent(s) tailored for individual patients.