Reciprocal activities between herpes simplex virus type 1 regulatory protein ICP0, a ubiquitin E3 ligase, and ubiquitin-specific protease USP7
Reciprocal activities between herpes simplex virus type 1 regulatory protein ICP0, a ubiquitin E3 ligase, and ubiquitin-specific protease USP7
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DOI：
10.1128/jvi.79.19.12342-12354.2005
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发表时间：
2005-10-01
影响因子：
5.4
通讯作者：
Everett, RD
中科院分区：
文献类型：
--
作者：
Boutell, C;Canning, M;Everett, RD
单纯疱疹病毒1型(HSV-1)调节蛋白ICP0刺激裂解感染和静止病毒基因组的重新激活。ICP0的这些作用需要它的环指E3泛素连接酶结构域，该结构域可以诱导几种细胞蛋白的降解，包括早幼粒白血病核体和着丝粒的成分。ICP0还与细胞泛素特异性蛋白酶USP7(也称为Hausp)相互作用非常强。我们以前已经证明，ICP0以一种环指依赖的方式诱导自己的泛素化和降解，并且它与USP7的相互作用调节这一过程。在这些研究过程中，我们发现并在此报告，ICP0还针对USP7进行泛素化和蛋白酶体依赖的降解。这两种蛋白的相互作用揭示了一个耐人寻味的情况，提出了在产生性HSV-1感染过程中这两个过程的平衡问题。基于对一株表达不能与USP7结合的ICP0形式的HSV-1突变病毒的特性的深入分析，我们得出结论：在产生性HSV-1感染过程中，USP7介导的ICP0的稳定优于ICP0诱导的USP7的降解。我们认为，ICP0-USP7相互作用的生物学意义可能在自然感染情况下最为明显，在这种情况下，ICP0的表达是有限的。
Herpes simplex virus type 1 (HSV-1) regulatory protein ICP0 stimulates lytic infection and the reactivation of quiescent viral genomes. These roles of ICP0 require its RING finger E3 ubiquitin ligase domain, which induces the degradation of several cellular proteins, including components of promyelocytic leukemia nuclear bodies and centromeres. ICP0 also interacts very strongly with the cellular ubiquitin-specific protease USP7 (also known as HAUSP). We have shown previously that ICP0 induces its own ubiquitination and degradation in a RING finger-dependent manner, and that its interaction with USP7 regulates this process. In the course of these studies we found and report here that ICP0 also targets USP7 for ubiquitination and proteasome-dependent degradation. The reciprocal activities of the two proteins reveal an intriguing situation that poses the question of the balance of the two processes during productive HSV-1 infection. Based on a thorough analysis of the properties of an HSV-1 mutant virus that expresses forms of ICP0 that are unable to bind to USP7, we conclude that USP7-mediated stabilization of ICP0 is dominant over ICP0-induced degradation of USP7 during productive HSV-1 infection. We propose that the biological significance of the ICP0-USP7 interaction may be most pronounced in natural infection situations, in which limited amounts of ICP0 are expressed.