Drug Development Targeting the Ubiquitin–Proteasome System (UPS) for the Treatment of Human Cancers
Abstract
Cancer cells are characterized by a higher rate of protein turnover and greater demand for protein homeostasis compared to normal cells. In this scenario, the ubiquitin–proteasome system (UPS), which is responsible for the degradation of over 80% of cellular proteins within mammalian cells, becomes vital to cancer cells, making the UPS a critical target for the discovery of novel cancer therapeutics. This review systematically categorizes all current reported small molecule inhibitors of the various essential components of the UPS, including ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), ubiquitin ligases (E3s), the 20S proteasome catalytic core particle (20S CP) and the 19S proteasome regulatory particles (19S RP), as well as their mechanism/s of action and limitations. We also discuss the immunoproteasome which is considered as a prospective therapeutic target of the next generation of proteasome inhibitors in cancer therapies.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 07, 2020
- Source ID
- 10.3390/cancers12040902
Entities
People
- Martina Bazzaro
- Stig Linder
- Xiaonan Zhang
Organizations
- Minnesota Ovarian Cancer Alliance
- National Institutes of Health Clinical Center
- United States Department of Defense