Abstract
Protein degradation is one of the tactics employed by the cell for irreversibly inactivating proteins. In eukaryotes, ATP-dependent protein degradation in the cytoplasm and nucleus is carried out by the 26S proteasome. Most proteins are targeted to the 26S proteasome by covalent attachment of a multi-ubiquitin chain. A key component of the enzyme cascade that results in attachment of the multi-ubiquitin chain to the target or labile protein is the ubiquitin ligase that controls the specificity of the ubiquitination reaction. Defects in ubiquitin-dependent proteolysis have been shown to result in a variety of human diseases, including cancer, neurodegenerative diseases, and metabolic disorders. This review focuses on the role of ubiquitin-dependent degradation in human disease and potential clinical applications that are being developed to exploit the cells natural proteolytic machinery to treat diseases.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Alzheimer Disease / metabolism
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Angelman Syndrome / metabolism
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Cystic Fibrosis / genetics
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Cystic Fibrosis / metabolism
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Female
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GTP-Binding Proteins / metabolism
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Hepatolenticular Degeneration / genetics
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Hepatolenticular Degeneration / metabolism
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Humans
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Ligases / metabolism
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Male
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Models, Biological
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Neoplasms / drug therapy
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Neoplasms / metabolism
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Parkinson Disease / genetics
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Parkinson Disease / metabolism
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Peptide Synthases / metabolism
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Proteins / chemistry
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Proteins / genetics
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Proteins / metabolism*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-cbl
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SKP Cullin F-Box Protein Ligases
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Ubiquitin / metabolism*
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Ubiquitin-Protein Ligases
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Uterine Cervical Neoplasms / metabolism
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beta-Transducin Repeat-Containing Proteins
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von Hippel-Lindau Disease / genetics
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von Hippel-Lindau Disease / metabolism
Substances
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BTRC protein, human
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Proteins
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Proto-Oncogene Proteins
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Ubiquitin
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beta-Transducin Repeat-Containing Proteins
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Proto-Oncogene Proteins c-cbl
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SKP Cullin F-Box Protein Ligases
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Ubiquitin-Protein Ligases
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GTP-Binding Proteins
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Ligases
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CBL protein, human
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Peptide Synthases