Cellular and disease functions of the Prader-Willi Syndrome gene MAGEL2.
Cellular and disease functions of the Prader-Willi Syndrome gene MAGEL2.
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DOI：
10.1042/bcj20160616
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发表时间：
2017-06-16
期刊：
影响因子：
--
通讯作者：
Potts PR
中科院分区：
文献类型：
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作者：
Tacer KF;Potts PR
黑素瘤抗原L2（MAGEL 2或MAGE-L2）是泛素连接酶调节剂的法师家族的成员。在相关的神经发育综合征，Prader-Willi综合征（PWS）和Schaaf-Yang综合征（SHFYNG）中，它是母系印记的，通常是父系缺失或突变的。MAGEL 2在下丘脑中高度表达，并且在通过逆转录分子分选途径从内体清除膜蛋白的基本细胞过程中起重要作用。MAGEL 2是由MAGEL 2、TRIM 27 E3泛素连接酶和USP 7去泛素化酶组成的多亚基蛋白复合物的一部分。MAGEL 2-USP 7-TRIM 27（或MUST）复合物通过WASH肌动蛋白成核促进因子的泛素化和活化促进逆转录聚合物再循环途径。本文综述了泛素连接酶调节剂的法师蛋白家族，并详细介绍了MAGEL 2在泛素化、肌动蛋白调节和内体分选过程中的分子和细胞作用，以及MAGEL 2在PWS和SHFYNG疾病中的意义，并通过对MAGEL 2基因敲除小鼠模型的研究阐明了其生理功能。
Melanoma antigen L2 (MAGEL2 or MAGE-L2) is a member of the MAGE family of ubiquitin ligase regulators. It is maternally imprinted and often paternally deleted or mutated in the related neurodevelopmental syndromes, Prader-Willi Syndrome (PWS) and Schaaf-Yang Syndrome (SHFYNG). MAGEL2 is highly expressed in the hypothalamus and plays an important role in a fundamental cellular process that recycles membrane proteins from endosomes through the retromer sorting pathway. MAGEL2 is part of a multi-subunit protein complex consisting of MAGEL2, the TRIM27 E3 ubiquitin ligase, and the USP7 deubiquitinating enzyme. The MAGEL2-USP7-TRIM27 (or MUST) complex facilitates the retromer recycling pathway through ubiquitination and activation of the WASH actin nucleation promoting factor. This review provides an overview of the MAGE protein family of ubiquitin ligases regulators and details the molecular and cellular role of MAGEL2 in ubiquitination, actin regulation, and endosomal sorting processes, as well as MAGEL2 implications in PWS and SHFYNG disorders and its physiological functions elucidated through the study of Magel2 knockout mouse models.