Abstract
The ubiquitin proteasome system (UPS) is critical for the regulation of many intracellular processes necessary for cell function and survival. The absolute requirement of the UPS for the maintenance of protein homeostasis and thereby for the regulation of protein quality control is reflected by the fact that deviation of proteasome function from the norm was reported in cardiovascular pathologies. Inflammation is a major factor contributing to cardiac pathology. Herein, cytokines induce protein translation and the production of free radicals, thereby challenging the cellular protein equilibrium. Here, we discuss current knowledge on the mechanisms of UPS-functional adaptation in response to oxidative stress in cardiac inflammation. The increasing pool of oxidant-damaged degradation-prone proteins in cardiac pathology accounts for the need for enhanced protein turnover by the UPS. This process is accomplished by an up-regulation of the ubiquitylation machinery and the induction of immunoproteasomes. Thereby, the inflamed heart muscle is cleared from accumulating misfolded proteins. Current advances on immunoproteasome-specific inhibitors in this field question the impact of the proteasome as a therapeutic target in heart failure.
Highlights
THE UBIQUITIN PROTEASOME SYSTEM The ubiquitin proteasome system (UPS) plays a central role in cellular protein-quality control, and MHC class I antigen presentation in viral infection
The 26S proteasome represents the essential catalytic part of the UPS that regulates the degradation of such ubiquitin-tagged protein substrates
The standard-20S catalytic core complex is built up from 28 subunits that are arranged as four heteroheptameric rings in a α1–7(β1–7)2α1–7 structure
Summary
THE UBIQUITIN PROTEASOME SYSTEM The ubiquitin proteasome system (UPS) plays a central role in cellular protein-quality control, and MHC class I antigen presentation in viral infection. Thereby, the efficient substrate ubiquitylation of oxidant-damaged and/or other misfolded nascent proteins in the cellular stress response ensures sufficient tagging of these degradation-prone products to be detected by 19S subunits of the 26S proteasome.
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