The proteasome system in the cell degrades the majority of intracellular proteins. The broad nature of its substrates makes proteasome activity crucial for many cellular functions, such as protein quality control, transcription, apoptosis, immune responses, cell signaling and differentiation. The proteasome system is thus an effective therapeutic target for malignant and non-malignant diseases. In this mini-review, we would like to highlight that proteasome function has also the potential to serve as a biomarker for disease severity and response to treatment. This notion is based on the observation that the six catalytic sites of the proteasome are distinctly altered in peripheral immune cells of patients with chronic inflammatory and autoimmune diseases. We here propose that proteasome activity can be profiled using minimally invasive peripheral blood samples to model severity, progression, and exacerbation of chronic inflammatory diseases. Moreover, the differential alteration of the catalytic activities of the proteasome points towards the existence of multiple catalytic forms of the 20S proteasome that potentially have distinct functions in immune cells. Understanding the role of the distinct immunoproteasome and intermediate proteasome complexes for immune cell function will pave the way for the application of site-specific immunoproteasome inhibitors to specifically target unwanted immune cell functions.
Activity-based Probes, Biomarker, Clinical immunology, PBMC, Proteasome