Cancer-testis antigen MAGE-C2 binds Rbx1 and inhibits ubiquitin ligase-mediated turnover of cyclin E |
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Authors: | Jiaqing Hao Xiao Song Jingjing Wang Chengli Guo Yan Li Bing Li Yu Zhang Yanhui Yin |
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Institution: | 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 |
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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. |
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Keywords: | cancer-testis antigen MAGE-C2 SCF complex cyclin E cell cycle |
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