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World J Clin Oncol. 2013 Aug 10;4(3):58-69. doi: 10.5306/wjco.v4.i3.58.

Role of E3 ubiquitin ligases in lung cancer.

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  • 1Barbara C Snoek, Leonie HAM de Wilt, Godefridus J Peters, Department of Medical Oncology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands.


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.


Apoptosis; Bortezomib; DNA repair; E3 ubiquitin ligases; Gene regulation; Lung cancer; Proteasome inhibitors; Ubiquitin-proteasome system

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