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The ubiquitin system serves protein modification and thereby regulates many essential cellular processes. An example is the induced endothelial dysfunction. It plays a crucial role in the pathophysiology of sepsis and organ failure. The underlying cause of sepsis is the host's overwhelming inflammatory response to the pathogen infection, leading to endothelial dysfunction. As the key factors of the ubiquitin system, E3 ligases are at the center of the battle between host and microbial pathogens. Such…