Cancer-testis antigen MAGE-C2 binds Rbx1 and inhibits ubiquitin ligase-mediated turnover of cyclin E.
Cancer-testis antigen MAGE-C2 binds Rbx1 and inhibits ubiquitin ligase-mediated turnover of cyclin E.
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DOI：
10.18632/oncotarget.5973
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发表时间：
2015-12-08
期刊：
影响因子：
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通讯作者：
Yin Y
中科院分区：
文献类型：
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作者：
Hao J;Song X;Wang J;Guo C;Li Y;Li B;Zhang Y;Yin Y
肿瘤-睾丸抗原MAGE-C2在睾丸中正常表达，但在多种肿瘤中异常表达。它在肿瘤细胞中的功能大多是未知的。在这里，我们表明MAGE-C2直接结合到RING结构域蛋白Rbx 1，并参与Skp 1-Cullin 1-F盒蛋白（SCF）复合物。此外，MAGE-C2可抑制SCF复合物的E3泛素连接酶活性。内源性MAGE-C2的消融通过抑制泛素介导的蛋白酶体降解降低细胞周期蛋白E的水平并加速细胞周期蛋白E的周转。MAGE-C2的过表达增加了细胞周期蛋白E的水平，并促进了G1-S转换和细胞增殖，该结果进一步被MAGE-C2的敲低所证实。总之，该研究表明MAGE-C2参与SCF复合物并增加肿瘤细胞中细胞周期蛋白E的稳定性。
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.