Translational research : the journal of laboratory and clinical medicine
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The present review aims to summarize available knowledge on the role of the ubiquitin-proteasome system (UPS) in the pathogenesis of scleroderma and scleroderma-related disease mechanisms. This will provide the reader with a more mechanistic understanding of disease pathogenesis and help to identify putative novel targets within the UPS for potential therapeutic intervention. Because of the heterogenous manifestations of scleroderma, we will primarily focus on conserved mechanisms that are involved in the development of lung scleroderma phenotypes.
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Cell homeostasis requires precise coordination of cellular proteins function. Ubiquitination is a post-translational modification that modulates protein half-life and function and is tightly regulated by ubiquitin E3 ligases and deubiquitinating enzymes. ⋯ Ubiquitination plays an important role in the pathobiology of acute lung injury as it regulates the proteins modulating the alveolocapillary barrier and the inflammatory response. Better understanding of the signaling pathways regulated by ubiquitination may lead to novel therapeutic approaches by targeting specific elements of the ubiquitination pathways.