Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2015; 21(3): 786-793
Published online Jan 21, 2015. doi: 10.3748/wjg.v21.i3.786
Role of E3 ubiquitin ligases in gastric cancer
Ya-Chao Hou, Jing-Yu Deng
Ya-Chao Hou, Jing-Yu Deng, Department of Gastroenterology, Cancer Hospital of Tianjin Medical University, City Key Laboratory of Tianjin Cancer Center, and National Clinical Research Center of Cancer, Tianjin 300060, China
Author contributions: Hou YC and Deng JY contributed equally to this work; Hou YC wrote the paper; and Deng JY designed the research.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jing-Yu Deng, MD, PhD, Department of Gastroenterology, Cancer Hospital of Tianjin Medical University, City Key Laboratory of Tianjin Cancer Center, and National Clinical Research Center of Cancer, Huanhuxi Road, Hexi District, Tianjin 300060, China. dengery@126.com
Telephone: +86-22-23340123 Fax: +86-22-23359904
Received: September 1, 2014
Peer-review started: September 7, 2014
First decision: October 14, 2014
Revised: November 1, 2014
Accepted: December 1, 2014
Article in press: December 1, 2014
Published online: January 21, 2015
Abstract

E3 ubiquitin ligases have an important role in carcinogenesis and include a large family of proteins that catalyze the ubiquitination of many protein substrates for targeted degradation by the 26S proteasome. So far, E3 ubiquitin ligases have been reported to have a role in a variety of biological processes including cell cycle regulation, cell proliferation, and apoptosis. Recently, several kinds of E3 ubiquitin ligases were demonstrated to be generally highly expressed in gastric cancer (GC) tissues and to contribute to carcinogenesis. In this review, we summarize the current knowledge and information about the clinical significance of E3 ubiquitin ligases in GC. Bortezomib, a proteasome inhibitor, encouraged the evaluation of other components of the ubiquitin proteasome system for pharmaceutical intervention. The clinical value of novel treatment strategies targeting aberrant E3 ubiquitin ligases for GC are discussed in the review.

Keywords: E3 ubiquitin ligases, Gastric cancer, Oncogene, Tumor suppressor gene, Target therapy

Core tip: E3 biquitin ligases are a large family of proteins that catalyze the ubiquitination of many protein substrates for targeted degradation by the 26S proteasome. They play an essential role in a variety of biological processes, including cell cycle regulation, proliferation and apoptosis. They are often found overexpressed in gastric cancer (GC) and their deregulation has been shown to contribute to GC development. The mechanisms of E3 ubiquitin ligases in the regulation of biological functions and their exact roles in carcinogenesis can help to develop specific E3 ubiquitin ligase inhibitors to improve the treatment strategies for GC patients.