Porcine circovirus type 2 ORF3 protein competes with P53 in binding to Pirh2 and mediates the deregulation of P53 homeostasis
Porcine circovirus type 2 ORF3 protein competes with P53 in binding to Pirh2 and mediates the deregulation of P53 homeostasis
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DOI：
10.1016/j.virol.2009.11.028
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发表时间：
2010-03-01
期刊：
影响因子：
3.7
通讯作者：
Kwang, Jimmy
中科院分区：
文献类型：
--
作者：
Karuppannan, Anbu K.;Liu, Sen;Kwang, Jimmy
猪圆环病毒 2 型 (PCV2) 的 ORF3 蛋白会导致病毒感染的细胞凋亡，但对于病毒复制不是必需的。 ORF3蛋白在小鼠模型和SPF仔猪PCV2感染的发病机制中发挥着重要作用。 ORF3 蛋白与 Pirh2 (pPirh2) 的猪同源物相互作用，Pirh2 是一种 p53 诱导的泛素蛋白 E3 连接酶，可调节 p53 泛素化。在这里，我们提出了我们的研究，分析了这三个因素之间分子相互作用的细节。我们的体外和体内实验表明，ORF3 蛋白与 p53 竞争与 pPirh2 的结合。 ORF3 蛋白的氨基酸残基 20 至 65 在 ORF3 蛋白与 pPirh2 而非 p53 的竞争性相互作用中至关重要。 ORF3蛋白与pPirh2的相互作用也导致pPirh2生理细胞定位的改变以及pPirh2稳定性的显着降低。这些事件导致 pPirh2 对 p53 的失调，导致 p53 水平增加和受感染细胞凋亡。 (C) 2009 Elsevier Inc. 保留所有权利。
The ORF3 protein of porcine circovirus type 2 (PCV2) causes apoptosis in virus-infected cells and is not essential for virus replication. The ORF3 protein plays an important role in the pathogenesis of the PCV2 infection in mouse models and SPF piglets. The ORF3 protein interacts with the porcine homologue of Pirh2 (pPirh2), a p53-induced ubiquitin-protein E3 ligase, which regulates p53 ubiquitination. Here, we present our study analyzing the details of the molecular interaction between these three factors. Our experiments, in vitro and in vivo, show that ORF3 protein competes with p53 in binding to pPirh2. The amino acid residues 20 to 65 of the ORF3 protein are essential in this competitive interaction of ORF3 protein with pPirh2 over p53. The interaction of ORF3 protein with pPirh2 also leads to an alteration in the physiological cellular localization of pPirh2 and a significant reduction in the stability of pPirh2. These events contribute to the deregulation of p53 by pPirh2, leading to increased p53 levels and apoptosis of the infected cells. (C) 2009 Elsevier Inc. All rights reserved.