Ubiquitin C-Terminal Hydrolase L1 in Tumorigenesis

• Type of Material: Article
• Authors: Jennifer Hurst-Kennedy, Emory University; Lih-Shen Chin, Emory University; Lian Li, Emory University
• Language: English
• Date: 2012-05-01
• Publisher: Hindawi Publishing Corporation
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Jennifer Hurst-Kennedy et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://www.hindawi.com/journals/bcri/2012/123706/
• Title of Journal or Parent Work: Biochemistry Research International
• ISSN: 2090-2247
• Volume: 2012
• Issue: 2012
• Start Page: 1
• End Page: 10
• Grant/Funding Information: This work was supported by National Institutes of Health grants NS050650 (L. S. Chin), AG034126 (L. S. Chin), ES015813 (L. Li), and GM082828 (L. Li) and by Fellowships in Research and Science Teaching (Institutional Research and Academic Career Development Award, 5K12GM000680).
• Research Categories: Chemistry, Biochemistry

Abstract

Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1, aka PGP9.5) is an abundant, neuronal deubiquitinating enzyme that has also been suggested to possess E3 ubiquitin-protein ligase activity and/or stabilize ubiquitin monomers in vivo. Recent evidence implicates dysregulation of UCH-L1 in the pathogenesis and progression of human cancers. Although typically only expressed in neurons, high levels of UCH-L1 have been found in many nonneuronal tumors, including breast, colorectal, and pancreatic carcinomas. UCH-L1 has also been implicated in the regulation of metastasis and cell growth during the progression of nonsmall cell lung carcinoma, colorectal cancer, and lymphoma. Together these studies suggest UCH-L1 has a potent oncogenic role and drives tumor development. Conversely, others have observed promoter methylation-mediated silencing of UCH-L1 in certain tumor subtypes, suggesting a potential tumor suppressor role for UCH-L1. In this paper, we provide an overview of the evidence supporting the involvement of UCH-L1 in tumor development and discuss the potential mechanisms of action of UCH-L1 in oncogenesis.