The Immunoproteasome: An Emerging Therapeutic Target

Wooin      Lee; Kyung      Bo Kim

Abstract

The proteasome, a large multisubunit protease complex, has been extensively investigated over the years, greatly enhancing our understanding of critical roles that the proteasome plays in cells. The FDA approval of bortezomib for the treatment of multiple myeloma and mantle cell lymphoma has validated the proteasome as an anticancer target. However, the undesirable toxicities of these agents limit their broad utility. The immunoproteasome, an alternative form of the constitutive proteasome, has recently been explored as a therapeutic target. While the immunoproteasome, normally expressed in cells of hematopoietic origin, has been shown to be associated with various types of cancer and inflammatory diseases, its multifaceted function is not fully understood due to the lack of appropriate molecular probes. In this review, recent advances in the immunoproteasome field are covered, including potential implications in disease states. In particular, recent developments in immunoproteasome-specific inhibitors are emphasized.

Keywords: Immunoproteasome, protein degradation, cancer, inhibitor, degenerative disease, molecular probes, immunoproteasome-specific inhibitors, ubiquitin, –, proteasome system (UPS), proteasome inhibitor, Polyubiquitinated proteins, amino acid polypeptide, immunoproteasome subunits, lymphocytic choriomeningitis virus, human prostate cancer