摘要
泛素系统控制蛋白质的稳定性和功能。F-box蛋白形成SCF(skp1-cullin1-f-box蛋白)型泛素连接酶(E3)通过泛素蛋白酶体途径选择性作用于底物的降解的。在这篇综述中,我们回顾F-box蛋白与癌症的发展。S-期激酶相关蛋白2(SKP2)(也被称为FBXL1)往往在人类癌症中过度表达,并作为一种致癌的E3连接酶降解抑癌基因产物。此外,含蛋白质7的F-box / WD重复(FBXW7)(也被称为Fbw7)往往在人类癌症中是经常突变的且其有一种靶向致癌蛋白降解肿瘤抑制E3连接酶的功能。Skp2在癌症治疗中是一个潜在的药物靶点,FBXW7在确定病人的诊断、预后及药物敏感性是有用的。在这篇综述中,我们还讨论了其他F-box蛋白参与癌症相关的细胞过程,如细胞周期调控、表观遗传调控,上皮间质转化,细胞凋亡/生存,耐药性,和DNA损伤的反应。
关键词: β- -TrCP 泛素连接酶,E3连接酶,F-box蛋白,抑癌基因FBXW7,人类癌症,蛋白酶体,SCF复合体,S期激酶相关蛋白Skp2,泛素
Current Cancer Drug Targets
Title:The SCF-type E3 Ubiquitin Ligases as Cancer Targets
Volume: 16 Issue: 2
Author(s): Kyoko Kitagawa and Masatoshi Kitagawa
Affiliation:
关键词: β- -TrCP 泛素连接酶,E3连接酶,F-box蛋白,抑癌基因FBXW7,人类癌症,蛋白酶体,SCF复合体,S期激酶相关蛋白Skp2,泛素
摘要: The ubiquitin system controls protein stability and function. F-box proteins form SCF (SKP1-Cullin1-F-box protein)-type ubiquitin (E3) ligases to selectively target their substrates for degradation via the ubiquitin–proteasome pathway. Here, we review F-box proteins associated with cancer development. S-phase kinase-associated protein 2 (SKP2) (also known as FBXL1) is often overexpressed in human cancers, and functions as an oncogenic E3 ligase to degrade tumor suppressor gene products. Moreover, F-box/WD repeat-containing protein 7 (FBXW7) (also known as Fbw7) is often mutated in human cancers and functions as a tumor suppressive E3 ligase targeting oncogenic proteins for degradation. SKP2 is a potential drug target for cancer therapy and FBXW7 is useful in determining patient diagnosis, prognosis, and drug sensitivity. In this review, we also discuss other F-box proteins involved in cancer-associated cellular processes such as cell cycle control, epigenetic regulation, epithelial mesenchymal transition, apoptosis/survival, drug resistance, and DNA-damage responses.
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Cite this article as:
Kyoko Kitagawa and Masatoshi Kitagawa , The SCF-type E3 Ubiquitin Ligases as Cancer Targets, Current Cancer Drug Targets 2016; 16 (2) . https://dx.doi.org/10.2174/1568009616666151112122231
DOI https://dx.doi.org/10.2174/1568009616666151112122231 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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