A Comprehensive Atlas of E3 Ubiquitin Ligase Mutations in Neurological Disorders.
A Comprehensive Atlas of E3 Ubiquitin Ligase Mutations in Neurological Disorders.
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DOI：
10.3389/fgene.2018.00029
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发表时间：
2018
影响因子：
3.7
通讯作者：
Mabb AM
中科院分区：
文献类型：
--
作者：
George AJ;Hoffiz YC;Charles AJ;Zhu Y;Mabb AM
蛋白质泛素化是一种翻译后修饰，在介导多种细胞功能中起着不可或缺的作用。蛋白质泛素化的过程需要一个酶级联反应，包括泛素活化酶（E1）、泛素缀合酶（E2）和E3泛素连接酶（E3）。估计有600-700个E3连接酶基因，约占人类基因组的5%。毫不奇怪，在多种神经系统疾病中观察到E3连接酶基因突变。我们构建了一个全面的图谱破坏E3连接酶基因在常见的（CND）和罕见的神经系统疾病（RND）。在预测和已知的人类E3连接酶基因中，我们发现约13%在神经系统疾病中发生突变，共有83个基因代表70种不同类型的神经系统疾病。在鉴定的E3连接酶基因中，51个与RND相关。在这里，我们提供了与E3连接酶基因破坏相关的神经系统疾病的最新列表。我们进一步强调这些神经系统疾病的研究，并讨论用于支持这些发现的先进技术。
Protein ubiquitination is a posttranslational modification that plays an integral part in mediating diverse cellular functions. The process of protein ubiquitination requires an enzymatic cascade that consists of a ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2) and an E3 ubiquitin ligase (E3). There are an estimated 600–700 E3 ligase genes representing ~5% of the human genome. Not surprisingly, mutations in E3 ligase genes have been observed in multiple neurological conditions. We constructed a comprehensive atlas of disrupted E3 ligase genes in common (CND) and rare neurological diseases (RND). Of the predicted and known human E3 ligase genes, we found ~13% were mutated in a neurological disorder with 83 total genes representing 70 different types of neurological diseases. Of the E3 ligase genes identified, 51 were associated with an RND. Here, we provide an updated list of neurological disorders associated with E3 ligase gene disruption. We further highlight research in these neurological disorders and discuss the advanced technologies used to support these findings.