Review
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World J Clin Oncol. Aug 10, 2013; 4(3): 58-69
Published online Aug 10, 2013. doi: 10.5306/wjco.v4.i3.58
Role of E3 ubiquitin ligases in lung cancer
Barbara C Snoek, Leonie HAM de Wilt, Gerrit Jansen, Godefridus J Peters
Barbara C Snoek, Leonie HAM de Wilt, Godefridus J Peters, Department of Medical Oncology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands
Gerrit Jansen, Department of Rheumatology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands
Author contributions: All authors contributed to conception of this paper; Snoek BC performed the initial literature search, which was updated by the other authors; Snoek BC made the initial concept of the paper; de Wilt LHAM revised the initial concept of the paper; Jansen G and Peters GJ provided additional comments and (re)wrote parts of the paper; all authors approved the final version.
Correspondence to: Godefridus J Peters, PhD, Department of Medical Oncology, VU University Medical Center, CCA 1.40, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. gj.peters@vumc.nl
Telephone: +31-20-4442633 Fax: +31-20-4443844
Received: December 3, 2012
Revised: May 27, 2013
Accepted: June 5, 2013
Published online: August 10, 2013
Processing time: 214 Days and 20.1 Hours
Abstract

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.

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

Core tip: E3 ubiquitin ligases catalyze ubiquitination of proteins for degradation by the 26S proteasome. They are important for many biological processes including cell cycle regulation, proliferation and apoptosis. They are often overexpressed and deregulated in lung cancer, which contributes to cancer development. These processes underline their potential as anti-cancer targets. There is only one E3 ubiquitin ligase inhibitor in clinical trial. A better understanding of how E3 ubiquitin ligases regulate biological processes and of their exact role in carcinogenesis, will help to develop specific E3 ubiquitin ligase inhibitors to improve treatment strategies for cancer patients.