Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038, USA.
Mol Cell. 2010 Sep 24;39(6):963-74. doi: 10.1016/j.molcel.2010.08.029.
The melanoma antigen (MAGE) family consists of more than 60 genes, many of which are cancer-testis antigens that are highly expressed in cancer and play a critical role in tumorigenesis. However, the biochemical and cellular functions of this enigmatic family of proteins have remained elusive. Here, we identify really interesting new gene (RING) domain proteins as binding partners for MAGE family proteins. Multiple MAGE family proteins bind E3 RING ubiquitin ligases with specificity. The crystal structure of one of these MAGE-RING complexes, MAGE-G1-NSE1, reveals structural insights into MAGE family proteins and their interaction with E3 RING ubiquitin ligases. Biochemical and cellular assays demonstrate that MAGE proteins enhance the ubiquitin ligase activity of RING domain proteins. For example, MAGE-C2-TRIM28 is shown to target p53 for degradation in a proteasome-dependent manner, consistent with its tumorigenic functions. These findings define a biochemical and cellular function for the MAGE protein family.
黑色素瘤相关抗原（MAGE）家族由 60 多个基因组成，其中许多是癌症-睾丸抗原，在癌症中高度表达，在肿瘤发生中起关键作用。然而，这个神秘的蛋白家族的生化和细胞功能仍然难以捉摸。在这里，我们确定了真正有趣的新基因（RING）结构域蛋白作为 MAGE 家族蛋白的结合伴侣。多种 MAGE 家族蛋白特异性地与 E3 RING 泛素连接酶结合。其中一个 MAGE-RING 复合物，MAGE-G1-NSE1 的晶体结构揭示了 MAGE 家族蛋白及其与 E3 RING 泛素连接酶相互作用的结构见解。生化和细胞测定表明，MAGE 蛋白增强了 RING 结构域蛋白的泛素连接酶活性。例如，已经表明 MAGE-C2-TRIM28 通过蛋白酶体依赖性方式靶向 p53 进行降解，这与其致瘤功能一致。这些发现定义了 MAGE 蛋白家族的生化和细胞功能。
