Small molecules that target the ubiquitin system
Biochemical Society Transactions, vol. 48, pp. 479–497
Abstract
Eukaryotic life depends upon the interplay between vast networks of signaling pathways composed of upwards of 109-1010 proteins per cell. The integrity and normal operation of the cell requires that these proteins act in a precise spatial and temporal manner. The ubiquitin system is absolutely central to this process and perturbation of its function contributes directly to the onset and progression of a wide variety of diseases, including cancer, metabolic syndromes, neurodegenerative diseases, autoimmunity, inflammatory disorders, infectious diseases, and muscle dystrophies. Whilst the individual components and the overall architecture of the ubiquitin system have been delineated in some detail, how ubiquitination might be successfully targeted, or harnessed, to develop novel therapeutic approaches to the treatment of disease, currently remains relatively poorly understood. In this review, we will provide an overview of the current status of selected small molecule ubiquitin system inhibitors. We will further discuss the unique challenges of targeting this ubiquitous and highly complex machinery, and explore and highlight potential ways in which these challenges might be met.
Authors 3
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Leiden University Medical Center · Oncode Institute
Affiliation as printed
Department of Cell and Chemical Biology, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands
Oncode Institute, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Cell and Chemical Biology, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands
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Leiden University Medical Center · Oncode Institute
Affiliation as printed
Department of Cell and Chemical Biology, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands
Oncode Institute, Leiden University Medical Center, 2300 RC Leiden, The Netherlands