Nedd4 和 Nedd4-2：密切相关的泛素蛋白连接酶，具有不同的生理功能。
Nedd4 and Nedd4-2: closely related ubiquitin-protein ligases with distinct physiological functions.
机构信息
Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
出版信息
Cell Death Differ. 2010 Jan;17(1):68-77. doi: 10.1038/cdd.2009.84.
Abstract
The Nedd4 (neural precursor cell-expressed developmentally downregulated gene 4) family of ubiquitin ligases (E3s) is characterized by a distinct modular domain architecture, with each member consisting of a C2 domain, 2-4 WW domains, and a HECT-type ligase domain. Of the nine mammalian members of this family, Nedd4 and its close relative, Nedd4-2, represent the ancestral ligases with strong similarity to the yeast, Rsp5. In Saccharomyces cerevisiae Rsp5 has a key role in regulating the trafficking, sorting, and degradation of a large number of proteins in multiple cellular compartments. However, in mammals the Nedd4 family members, including Nedd4 and Nedd4-2, appear to have distinct functions, thereby suggesting that these E3s target specific proteins for ubiquitylation. In this article we focus on the biology and emerging functions of Nedd4 and Nedd4-2, and review recent in vivo studies on these E3s.
摘要
Nedd4（神经前体细胞表达的发育下调基因 4）家族的泛素连接酶（E3）的特征在于独特的模块化结构域架构，每个成员由一个 C2 结构域、2-4 个 WW 结构域和一个 HECT 型连接酶结构域组成。在该家族的九种哺乳动物成员中，Nedd4 及其近亲 Nedd4-2 代表了与酵母 Rsp5 具有很强相似性的祖先连接酶。在酿酒酵母中，Rsp5 在调节大量蛋白质在多个细胞区室中的运输、分拣和降解方面发挥着关键作用。然而，在哺乳动物中，Nedd4 家族成员，包括 Nedd4 和 Nedd4-2，似乎具有不同的功能，这表明这些 E3 针对特定蛋白质进行泛素化。本文重点介绍了 Nedd4 和 Nedd4-2 的生物学和新兴功能，并回顾了这些 E3 在体内的最新研究。
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Functional regulation of the epithelial Na+ channel by IkappaB kinase-beta occurs via phosphorylation of the ubiquitin ligase Nedd4-2.IκB激酶β通过泛素连接酶Nedd4-2的磷酸化作用对上皮钠离子通道进行功能调控。
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