Cancer-testis antigen MAGE-C2 binds Rbx1 and inhibits ubiquitin ligase-mediated turnover of cyclin E

Abstract

// Jiaqing Hao 1, * , Xiao Song 1, * , Jingjing Wang 1 , Chengli Guo 1 , Yan Li 1 , Bing Li 2 , Yu Zhang 1 , Yanhui Yin 1 1 Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China 2 Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA * These authors have contributed equally to this work Correspondence to: Yu Zhang, e-mail: zhangyu007@bjmu.edu.cn Yanhui Yin, e-mail: yinyanhui@bjmu.edu.cn Keywords: cancer-testis antigen, MAGE-C2, SCF complex, cyclin E, cell cycle Received: June 29, 2015      Accepted: October 09, 2015      Published: October 19, 2015 ABSTRACT Cancer-testis antigen MAGE-C2 is normally expressed in testis but aberrantly expressed in various kinds of tumors. Its functions in tumor cells are mostly unknown. Here, we show that MAGE-C2 binds directly to the RING domain protein Rbx1, and participates in Skp1-Cullin1-F box protein (SCF) complex. Furthermore, MAGE-C2 can inhibit the E3 ubiquitin ligase activity of SCF complex. Ablation of endogenous MAGE-C2 decreases the level of cyclin E and accelerates cyclin E turnover by inhibiting ubiquitin-mediated proteasome degradation. Overexpression of MAGE-C2 increases the level of cyclin E and promotes G1-S transition and cell proliferation, and the results are further confirmed by knockdown of MAGE-C2. Overall, the study indicates that MAGE-C2 is involved in SCF complex and increases the stability of cyclin E in tumor cells.