Regulation of Vaccinia Virus E3 Protein by Small Ubiquitin-Like Modifier Proteins
Regulation of Vaccinia Virus E3 Protein by Small Ubiquitin-Like Modifier Proteins
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DOI：
10.1128/jvi.05628-11
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发表时间：
2011-12-01
影响因子：
5.4
通讯作者：
Rivas, Carmen
中科院分区：
文献类型：
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作者：
Gonzalez-Santamaria, Jose;Campagna, Michela;Rivas, Carmen
痘苗病毒(VACV)E3蛋白是毒力所必需的，具有抗细胞凋亡活性和损害宿主天然免疫反应的能力。在这里，我们证明了E3通过一个小的泛素样修饰物(SUMO)相互作用基序(SIM)与SUMO1相互作用。SIM完整性是维持病毒蛋白稳定性和E3与SUMO1或SUMO2共价连接所必需的，这种修饰对P53上调的凋亡调节因子(PUMA)和APAF-1基因的E3转录反式激活具有负面影响。我们还证明了E3是泛素化的，这一修饰不会破坏野生型蛋白的稳定性，但会触发E3-Delta SIM突变体的降解。这份报告首次证明了相扑和泛素在VACV蛋白E3的调节中发挥的重要作用。
The vaccinia virus (VACV) E3 protein is essential for virulence and has antiapoptotic activity and the ability to impair the host innate immune response. Here we demonstrate that E3 interacts with SUMO1 through a small ubiquitin-like modifier (SUMO)-interacting motif (SIM). SIM integrity is required for maintaining the stability of the viral protein and for the covalent conjugation of E3 to SUMO1 or SUMO2, a modification that has a negative effect on the E3 transcriptional transactivation of the p53-upregulated modulator of apoptosis (PUMA) and APAF-1 genes. We also demonstrate that E3 is ubiquitinated, a modification that does not destabilize the wild-type protein but triggers the degradation of an E3-Delta SIM mutant. This report constitutes the first demonstration of the important roles that both SUMO and ubiquitin play in the regulation of the VACV protein E3.