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Journal of Immunology Research
Volume 2015, Article ID 541984, 8 pages
http://dx.doi.org/10.1155/2015/541984
Review Article

New Insights into the Function of the Immunoproteasome in Immune and Nonimmune Cells

1Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan
2Department of Pathology, The Johns Hopkins School of Medicine, Ross 656, 720 Rutland Avenue, Baltimore, MD 20205, USA
3Department of Clinical Laboratory Science, Faculty of Medical Science, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan

Received 10 July 2015; Accepted 10 September 2015

Academic Editor: Darren R. Flower

Copyright © 2015 Hiroaki Kimura et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The immunoproteasome is a highly efficient proteolytic machinery derived from the constitutive proteasome and is abundantly expressed in immune cells. The immunoproteasome plays a critical role in the immune system because it degrades intracellular proteins, for example, those of viral origin, into small proteins. They are further digested into short peptides to be presented by major histocompatibility complex (MHC) class I molecules. In addition, the immunoproteasome influences inflammatory disease pathogenesis through its ability to regulate T cell polarization. The immunoproteasome is also expressed in nonimmune cell types during inflammation or neoplastic transformation, supporting a role in the pathogenesis of autoimmune diseases and neoplasms. Following the success of inhibitors of the constitutive proteasome, which is now an established treatment modality for multiple myeloma, compounds that selectively inhibit the immunoproteasome are currently under active investigation. This paper will review the functions of the immunoproteasome, highlighting areas where novel pharmacological treatments that regulate immunoproteasome activity could be developed.