Snoek Barbara C, de Wilt Leonie Ham, Jansen Gerrit, Peters Godefridus J
Barbara C Snoek, Leonie HAM de Wilt, Godefridus J Peters, Department of Medical Oncology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands.
World J Clin Oncol. 2013 Aug 10;4(3):58-69. doi: 10.5306/wjco.v4.i3.58.
E3 ubiquitin ligases are a large family of proteins that catalyze the ubiquitination of many protein substrates for targeted degradation by the 26S proteasome. Therefore, E3 ubiquitin ligases play an essential role in a variety of biological processes including cell cycle regulation, proliferation and apoptosis. E3 ubiquitin ligases are often found overexpressed in human cancers, including lung cancer, and their deregulation has been shown to contribute to cancer development. However, the lack of specific inhibitors in clinical trials is a major issue in targeting E3 ubiquitin ligases with currently only one E3 ubiquitin ligase inhibitor being tested in the clinical setting. In this review, we focus on E3 ubiquitin ligases that have been found deregulated in lung cancer. Furthermore, we discuss the processes in which they are involved and evaluate them as potential anti-cancer targets. By better understanding the mechanisms by which E3 ubiquitin ligases regulate biological processes and their exact role in carcinogenesis, we can improve the development of specific E3 ubiquitin ligase inhibitors and pave the way for novel treatment strategies for cancer patients.
E3泛素连接酶是一大类蛋白质,可催化许多蛋白质底物的泛素化,以便被26S蛋白酶体靶向降解。因此,E3泛素连接酶在包括细胞周期调控、增殖和凋亡在内的多种生物学过程中发挥着至关重要的作用。E3泛素连接酶在包括肺癌在内的人类癌症中常常过度表达,并且已表明其失调会促进癌症发展。然而,临床试验中缺乏特异性抑制剂是靶向E3泛素连接酶的一个主要问题,目前在临床环境中仅有一种E3泛素连接酶抑制剂正在接受测试。在本综述中,我们聚焦于在肺癌中发现失调的E3泛素连接酶。此外,我们讨论它们所涉及的过程,并将它们评估为潜在的抗癌靶点。通过更好地理解E3泛素连接酶调节生物学过程的机制及其在致癌作用中的确切作用,我们可以改进特异性E3泛素连接酶抑制剂的研发,并为癌症患者的新型治疗策略铺平道路。