Published online Aug 10, 2013. doi: 10.5306/wjco.v4.i3.58
Revised: May 27, 2013
Accepted: June 5, 2013
Published online: August 10, 2013
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.
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.