Immune and non-immune functions of the immunoproteasome

Abstract

The biological importance of the ubiquitin-proteasome system in the control of myriad cellular processes has been well-recognized; however, the pathophysiological significance of the immunoproteasome, the inducible form of the proteasome, has not been well-comprehended until lately. The primary function of the immunoproteasome was originally believed to improve MHC-I antigen presentation. It now becomes evident that the immunoproteasome possesses broader biological functions. It regulates proinflammatory cytokine production, and T cell differentiation and proliferation. Alongside immune functions, the immunoproteasome has been demonstrated to relieve oxidative stress by the efficient turnover of oxidatively-damaged proteins and by allaying the formation of harmful protein aggregates. Furthermore, it has been implicated to regulate tumor cell growth and control muscle mass. Finally, the immunoproteasome has recently drawn considerable attention as a potential novel therapeutic target for cancer and autoimmune disease. This review will give an overview of the structure and function of the immunoproteasome, highlight its functional diversity in both immune and non-immune responses, and discuss the relationship between the dysregulation of the immunoproteasome and the development of several human diseases.

PGF2α levels in Day 8 blood plasma are increased by the presence of one or more embryos in the uterus

“…Clusterin, a protein associated with receptivity in mice (Brown et al, 1996), participates in hexose metabolism, antioxidative activity and protease activity. Immunoproteasome subunit 20S (β5i) (i20S) distinguishes proteasome activity from immunoproteasome activity (Angeles et al, 2012). The activation of proteasome/immunoproteasome subunits and the association of such a complex with factors linked to interferon-γ (IFNG; a close analogue to the ruminant IFNT) suggest that embryonic recognition at these early stages does not involve antigen processing and likely participation of interferons, contrary to the differences we previously observed between embryos of different sex (Gómez et al, 2013).…”

In Vitro and In Vivo Therapeutic Efficacy of Carfilzomib in Mantle Cell Lymphoma: Targeting the Immunoproteasome

“…efficiency of MHC-I antigen presentation in adaptive immune responses after IFNg stimulation (29,30). More recently, it has become evident that i-proteasome is constitutively expressed and possesses broader biologic functions in various types of cancer including hematologic malignancies (31,32).…”

Targeting the Ubiquitin-Proteasome System in Heart Disease: The Basis for New Therapeutic Strategies

“…The plural in the term ''20S proteasomes'' must be emphasized, because two populations are known since early on: a constitutive and an inducible form (71). Since its discovery, the inducible 20S proteasome is assigned a role in immune response and antigen processing, but more recent research associates it with broader function, including stress response and the degradation of proteins damaged by oxidation (3,11,119). In the mammalian heart, both 20S proteasome populations and subpopulations with mixed assembly exist under unstimulated conditions ( Fig.…”