Herpesviruses possess conserved proteins for interaction with Nedd4 family ubiquitin E3 ligases.
Herpesviruses possess conserved proteins for interaction with Nedd4 family ubiquitin E3 ligases.
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DOI：
10.1038/s41598-018-22682-2
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发表时间：
2018-03-13
影响因子：
4.6
通讯作者：
Suzutani T
中科院分区：
文献类型：
--
作者：
Koshizuka T;Kobayashi T;Ishioka K;Suzutani T
Nedd 4是一个泛素E3连接酶家族，调节许多细胞过程。在这份报告中，我们发现α-和β-疱疹病毒具有调节Nedd 4家族成员功能的膜蛋白。尽管同源性检索得分相当低，但单纯疱疹病毒1型和2型的UL 56、水痘-带状疱疹病毒的ORF 0、人巨细胞病毒的UL 42以及人疱疹病毒6A、6 B和7的U24在其胞质结构域中均具有至少一个PPxY（PY）基序，并且能够与Nedd 4家族的成员Itch结合。这些病毒蛋白改变了Itch的定位，并降低了共表达细胞中Itch的表达。此外，这些病毒蛋白通过调节Nedd 4蛋白家族减少逆转录病毒载体的产生。U24，而不是其他蛋白质，有效地降低了T细胞表面上的CD 3 ε表达。这些病毒分子被认为通过调节Nedd 4家族的活性来促进每种病毒的特定功能。
Nedd4 is a family of ubiquitin E3 ligases that regulate numerous cellular processes. In this report, we showed that alpha- and beta-herpesviruses have membrane proteins that regulate the function of the Nedd4 family members. Although the homology search score was quite low, UL56 of herpes simplex virus type 1 and 2, ORF0 of varicella-zoster virus, UL42 of human cytomegalovirus, and U24 of human herpesvirus 6A, 6B, and 7 all possess at least one PPxY (PY) motif in their cytoplasmic domain, and are able to bind with Itch, a member of the Nedd4 family. These viral proteins altered the localization of Itch and decreased Itch expression in co-expressing cells. In addition, these viral proteins reduced the production of retrovirus vectors through the regulation of the Nedd4 family of proteins. U24, but not the other proteins, effectively reduced CD3ε expression on the T cell surface. These viral molecules are thought to contribute to the specific function of each virus through the regulation of Nedd4 family activity.
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