Abstract
The F-box protein Fbw7 targets for degradation critical cellular regulators, thereby controlling essential processes in cellular homeostasis, including cell cycle, differentiation and apoptosis. Most Fbw7 substrates are strongly associated with tumorigenesis and Fbw7 can either suppress or promote tumor development in mouse models. Fbw7 activity is controlled at different levels, resulting in specific and tunable regulation of the abundance and activity of its substrates. Here we highlight recent studies on the role of Fbw7 in controlling tumorigenesis and on the mechanisms that modulate Fbw7 function.
Keywords:
Fbw7; Oncogene; Protein degradation; SCF ubiquitin ligase; Tumor suppressor.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Cell Cycle Proteins / chemistry
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Cell Cycle Proteins / genetics*
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Cell Cycle Proteins / metabolism*
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Cell Transformation, Neoplastic / genetics*
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Cell Transformation, Neoplastic / metabolism*
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F-Box Proteins / chemistry
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F-Box Proteins / genetics*
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F-Box Proteins / metabolism*
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F-Box-WD Repeat-Containing Protein 7
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Gene Expression Regulation, Neoplastic
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Homeostasis
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Humans
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Molecular Targeted Therapy
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Neoplasms / drug therapy
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Neoplasms / etiology*
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Neoplasms / metabolism*
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Neoplasms / pathology
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Protein Binding
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Protein Multimerization
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Protein Transport
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Proteolysis
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Signal Transduction
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Substrate Specificity
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Ubiquitin-Protein Ligases / chemistry
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Ubiquitin-Protein Ligases / genetics*
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Ubiquitin-Protein Ligases / metabolism*
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Ubiquitination
Substances
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Cell Cycle Proteins
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F-Box Proteins
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F-Box-WD Repeat-Containing Protein 7
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FBXW7 protein, human
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Ubiquitin-Protein Ligases