About this Journal Submit a Manuscript Table of Contents
TheScientificWorldJOURNAL
Volume 10 (2010), Pages 1001-1015
http://dx.doi.org/10.1100/tsw.2010.89
Mini-Review Article

Regulation of Skp2 Expression and Activity and Its Role in Cancer Progression

1Department of Molecular and Cellular Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA
2University of Texas, Graduate School of Biomedical Sciences, Houston, TX, USA

Received 31 January 2010; Revised 20 April 2010; Accepted 22 April 2010

Academic Editor: Adele Murrell

Copyright © 2010 Chia-Hsin Chan et al.

Abstract

The regulation of cell cycle entry is critical for cell proliferation and tumorigenesis. One of the key players regulating cell cycle progression is the F-box protein Skp2. Skp2 forms a SCF complex with Skp1, Cul-1, and Rbx1 to constitute E3 ligase through its F-box domain. Skp2 protein levels are regulated during the cell cycle, and recent studies reveal that Skp2 stability, subcellular localization, and activity are regulated by its phosphorylation. Overexpression of Skp2 is associated with a variety of human cancers, indicating that Skp2 may contribute to the development of human cancers. The notion is supported by various genetic mouse models that demonstrate an oncogenic activity of Skp2 and its requirement in cancer progression, suggesting that Skp2 may be a novel and attractive therapeutic target for cancers.