Research Papers:

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

Jiaqing Hao _, Xiao Song, Jingjing Wang, Chengli Guo, Yan Li, Bing Li, Yu Zhang and Yanhui Yin

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Oncotarget. 2015; 6:42028-42039. https://doi.org/10.18632/oncotarget.5973

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Jiaqing Hao1,*, Xiao Song1,*, Jingjing Wang1, Chengli Guo1, Yan Li1, Bing Li2, Yu Zhang1, Yanhui Yin1

1Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China

2Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA

*These authors have contributed equally to this work

Correspondence to:

Yu Zhang, e-mail: [email protected]

Yanhui Yin, e-mail: [email protected]

Keywords: cancer-testis antigen, MAGE-C2, SCF complex, cyclin E, cell cycle

Received: June 29, 2015     Accepted: October 09, 2015     Published: October 19, 2015


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.

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