Tumor Suppression by the Fbw7 Ubiquitin Ligase: Mechanisms and Opportunities
Tumor suppressors with widespread impact on carcinogenesis control broad spectra of oncogenic pathways. Protein degradation is an emerging mechanism by which tumor suppressors regulate a diversity of pathways and is exemplified by the SCFFbw7 ubiquitin ligase. Rapidly accumulating data indicate that...
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| Veröffentlicht in: | Cancer cell 2014-10, Vol.26 (4), p.455-464 |
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| container_title | Cancer cell |
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| creator | Davis, Ryan J. Welcker, Markus Clurman, Bruce E. |
| description | Tumor suppressors with widespread impact on carcinogenesis control broad spectra of oncogenic pathways. Protein degradation is an emerging mechanism by which tumor suppressors regulate a diversity of pathways and is exemplified by the SCFFbw7 ubiquitin ligase. Rapidly accumulating data indicate that SCFFbw7 regulates a network of crucial oncoproteins. Importantly, the FBXW7 gene, which encodes Fbw7, is one of the most frequently mutated genes in human cancers. These studies are yielding important new insights into tumorigenesis and may soon enable therapies targeting the Fbw7 pathway. Here, we focus on the mechanisms and consequences of Fbw7 deregulation in cancers and discuss possible therapeutic approaches. |
| doi_str_mv | 10.1016/j.ccell.2014.09.013 |
| format | Article |
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Protein degradation is an emerging mechanism by which tumor suppressors regulate a diversity of pathways and is exemplified by the SCFFbw7 ubiquitin ligase. Rapidly accumulating data indicate that SCFFbw7 regulates a network of crucial oncoproteins. Importantly, the FBXW7 gene, which encodes Fbw7, is one of the most frequently mutated genes in human cancers. These studies are yielding important new insights into tumorigenesis and may soon enable therapies targeting the Fbw7 pathway. Here, we focus on the mechanisms and consequences of Fbw7 deregulation in cancers and discuss possible therapeutic approaches.</description><identifier>ISSN: 1535-6108</identifier><identifier>EISSN: 1878-3686</identifier><identifier>DOI: 10.1016/j.ccell.2014.09.013</identifier><identifier>PMID: 25314076</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Cell Cycle Proteins - genetics ; Cell Cycle Proteins - physiology ; F-Box Proteins - genetics ; F-Box Proteins - physiology ; F-Box-WD Repeat-Containing Protein 7 ; Genes, Tumor Suppressor ; Humans ; Mutation ; Neoplasms - genetics ; Neoplasms - pathology ; Ubiquitin-Protein Ligases - genetics ; Ubiquitin-Protein Ligases - physiology</subject><ispartof>Cancer cell, 2014-10, Vol.26 (4), p.455-464</ispartof><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><rights>2014 Elsevier Inc. 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Protein degradation is an emerging mechanism by which tumor suppressors regulate a diversity of pathways and is exemplified by the SCFFbw7 ubiquitin ligase. Rapidly accumulating data indicate that SCFFbw7 regulates a network of crucial oncoproteins. Importantly, the FBXW7 gene, which encodes Fbw7, is one of the most frequently mutated genes in human cancers. These studies are yielding important new insights into tumorigenesis and may soon enable therapies targeting the Fbw7 pathway. Here, we focus on the mechanisms and consequences of Fbw7 deregulation in cancers and discuss possible therapeutic approaches.</description><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Cycle Proteins - physiology</subject><subject>F-Box Proteins - genetics</subject><subject>F-Box Proteins - physiology</subject><subject>F-Box-WD Repeat-Containing Protein 7</subject><subject>Genes, Tumor Suppressor</subject><subject>Humans</subject><subject>Mutation</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - pathology</subject><subject>Ubiquitin-Protein Ligases - genetics</subject><subject>Ubiquitin-Protein Ligases - physiology</subject><issn>1535-6108</issn><issn>1878-3686</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kNtKxDAQhoMoHlafQJC-QOskadJWUBDxBCteuF6HHGbdLLttTVrFt_FZfDKrq6I3Xs3A_AfmI2SfQkaBysN5Zi0uFhkDmmdQZUD5GtmmZVGmXJZyfdgFF6mkUG6RnRjnMLhoUW2SLSY4zaGQ2-Rm0i-bkNz1bRswRt_UiXlJuhkmF-a5eHu9N_6x952vk7F_0BGPkhu0M137uIyJrl1y27ZN6Pp60GDcJRtTvYi49zVH5P7ifHJ2lY5vL6_PTsepzYXoUjllXGio0FADjjJa5aJyiAUwVzmT51QbRmXOGZRiypAaUZWMlxyBg5OGj8jJKrftzRKdxboLeqHa4Jc6vKhGe_X3UvuZemieVM5YIaEcAvgqwIYmxoDTHy8F9UFXzdUnXfVBV0GlBrqD6-B37Y_nG-cgOF4JcHj-yWNQ0XqsLTof0HbKNf7fgndRCo4g</recordid><startdate>20141013</startdate><enddate>20141013</enddate><creator>Davis, Ryan J.</creator><creator>Welcker, Markus</creator><creator>Clurman, Bruce E.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20141013</creationdate><title>Tumor Suppression by the Fbw7 Ubiquitin Ligase: Mechanisms and Opportunities</title><author>Davis, Ryan J. ; Welcker, Markus ; Clurman, Bruce E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-6f235a09eb1b0d1219459dee702d9db441ab216432085f2e1b5982383e030d6b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Cycle Proteins - physiology</topic><topic>F-Box Proteins - genetics</topic><topic>F-Box Proteins - physiology</topic><topic>F-Box-WD Repeat-Containing Protein 7</topic><topic>Genes, Tumor Suppressor</topic><topic>Humans</topic><topic>Mutation</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - pathology</topic><topic>Ubiquitin-Protein Ligases - genetics</topic><topic>Ubiquitin-Protein Ligases - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Davis, Ryan J.</creatorcontrib><creatorcontrib>Welcker, Markus</creatorcontrib><creatorcontrib>Clurman, Bruce E.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Davis, Ryan J.</au><au>Welcker, Markus</au><au>Clurman, Bruce E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor Suppression by the Fbw7 Ubiquitin Ligase: Mechanisms and Opportunities</atitle><jtitle>Cancer cell</jtitle><addtitle>Cancer Cell</addtitle><date>2014-10-13</date><risdate>2014</risdate><volume>26</volume><issue>4</issue><spage>455</spage><epage>464</epage><pages>455-464</pages><issn>1535-6108</issn><eissn>1878-3686</eissn><abstract>Tumor suppressors with widespread impact on carcinogenesis control broad spectra of oncogenic pathways. 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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; EZB-FREE-00999 freely available EZB journals |
| subjects | Cell Cycle Proteins - genetics Cell Cycle Proteins - physiology F-Box Proteins - genetics F-Box Proteins - physiology F-Box-WD Repeat-Containing Protein 7 Genes, Tumor Suppressor Humans Mutation Neoplasms - genetics Neoplasms - pathology Ubiquitin-Protein Ligases - genetics Ubiquitin-Protein Ligases - physiology |
| title | Tumor Suppression by the Fbw7 Ubiquitin Ligase: Mechanisms and Opportunities |
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