Tumor Suppression by the Fbw7 Ubiquitin Ligase: Mechanisms and Opportunities

被引：296
作者：
Davis, Ryan J. [1 ,2 ,3 ]
Welcker, Markus [1 ,2 ]
Clurman, Bruce E. [1 ,2 ]
机构：
[1] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA
[2] Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98109 USA
[3] Univ Washington, Mol & Cellular Biol Program, Seattle, WA 98195 USA
来源：
CANCER CELL | 2014年 / 26卷 / 04期
基金：
美国国家科学基金会;
关键词：
F-BOX PROTEIN; ACUTE LYMPHOBLASTIC-LEUKEMIA; STEM-CELL DIFFERENTIATION; FBXW7; BETA-FORM; CYCLIN-E; C-MYC; DEPENDENT DEGRADATION; PROMOTER HYPERMETHYLATION; MULTISITE PHOSPHORYLATION; SUBSTRATE RECOGNITION;
D O I：
10.1016/j.ccell.2014.09.013
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
引用
收藏
页码：455 / 464
页数：10
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