F-box proteins: Keeping the epithelial-to-mesenchymal transition (EMT) in check

详细信息    查看全文

• 作者：Ví ; ctor M. Dí ; az^a ; ^b ; ^c ; ^{victor.diaz@upf.edu" class="auth_mail" title="E-mail the corresponding author} ; Antonio Garcí ; a de Herreros^a ; ^b ; ^c ; ^{agarcia@imim.es" class="auth_mail" title="E-mail the corresponding author}
• 关键词：EMT ; Snail ; Twist ; Zeb ; F-box ; Ubiquitination ; Proteasome ; Cancer
• 刊名：Seminars in Cancer Biology
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：36
• 期：Complete
• 页码：71-79
• 全文大小：2117 K

文摘

F-box proteins are the key recognition subunit of multimeric E3 ubiquitin ligase complexes that participate in the proteasome degradation of specific substrates. In the last years, a discrete number of F-box proteins have been shown to regulate the epithelial-to-mesenchymal transition (EMT), a process defined by a rapid change of cell phenotype, the loss of epithelial characteristics and the acquisition of a more invasive phenotype. Specific EMT transcription factors (EMT-TFs), such as Snail, Slug, Twist and Zeb, control EMT induction both during development and in cancer. These EMT-TFs are short-lived proteins that are targeted to the proteasome system by specific F-box proteins, keeping them at low levels. F-box proteins also indirectly regulate the EMT process by controlling EMT inducers, such as Notch, c-Myc or mTOR. Here we summarize the role that these F-box proteins (Fbxw1, Fbxw7, Fbxl14, Fbxl5, Fbxo11 and Fbxo45) play in controlling EMT during development and cancer progression, a process dependent on post-translational modifications that govern their interaction with target proteins.