MAGE-RING protein complexes comprise a family of E3 ubiquitin ligases.
MAGE-RING protein complexes comprise a family of E3 ubiquitin ligases.
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DOI：
10.1016/j.molcel.2010.08.029
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发表时间：
2010-09-24
期刊：
影响因子：
16
通讯作者：
Potts PR
中科院分区：
文献类型：
--
作者：
Doyle JM;Gao J;Wang J;Yang M;Potts PR
黑色素瘤抗原（MAGE）家族由60多个基因组成，其中许多是癌睾丸抗原，在癌症中高表达，在肿瘤发生中发挥关键作用。然而，这个神秘的蛋白质家族的生化和细胞功能仍然难以捉摸。在这里，我们确定了非常有趣的新基因 (RING) 结构域蛋白作为 MAGE 家族蛋白的结合伴侣。多个 MAGE 家族蛋白特异性结合 E3 RING 泛素连接酶。这些 MAGE-RING 复合物之一 MAGE-G1-NSE1 的晶体结构揭示了 MAGE 家族蛋白的结构见解及其与 E3 RING 泛素连接酶的相互作用。生化和细胞测定表明，MAGE 蛋白可增强 RING 结构域蛋白的泛素连接酶活性。例如，MAGE-C2-TRIM28 显示以 p53 为目标，以蛋白酶体依赖性方式降解，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。
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.