Deneddylation by SENP8 restricts hepatitis B virus propagation
Deneddylation by SENP8 restricts hepatitis B virus propagation
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DOI：
10.1111/1348-0421.12874
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发表时间：
2021-02-24
影响因子：
2.6
通讯作者：
Okamoto, Toru
中科院分区：
文献类型：
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作者：
Chen, David Virya;Suzuki, Tatsuya;Okamoto, Toru
由信使RNA新合成的蛋白质经历翻译后修饰（PTM），如磷酸化、糖基化、甲基化和泛素化。这些PTM在蛋白质稳定性、定位和构象中具有重要作用，并且已报道参与B型肝炎病毒（HBV）的传播。虽然泛素化在HBV的生命周期中起着重要的作用，但泛素样蛋白（UBLs）在HBV生命周期中的作用还没有得到充分的研究。通过对UBL进行全面的功能获得和功能丧失筛选，我们观察到，neddylation是一种PTM，其中神经前体细胞表达的发育下调8（NEDD8）与底物蛋白缀合，是HBV有效繁殖所需的。我们还发现，过表达sentrin特异性蛋白酶8（SENP 8），切割共轭NEDD 8，抑制HBV的传播。此外，SENP 8的催化活性是抑制HBV传播所必需的。这些结果表明，neddylation的减少负调控HBV的传播。此外，我们证明通过SENP 8过表达抑制HBV传播不依赖于B蛋白X（HBx）和HBV启动子活性。因此，我们的数据表明，neddylation在HBV生命周期的后期阶段起着重要作用。
Proteins newly synthesized from messenger RNA undergo Posttranslational modifications (PTMs) such as phosphorylation, glycosylation, methylation, and ubiquitination. These PTMs have important roles in protein stability, localization, and conformation and have been reported to be involved in hepatitis B virus (HBV) propagation. Although ubiquitination plays an essential role in HBV life cycles, the involvement of ubiquitin-like proteins (UBLs) in HBV life cycles has been understudied. Through comprehensive gain- and loss-of-function screening of UBLs, we observed that neddylation, a PTM in which neural precursor cell, expressed developmentally downregulated 8 (NEDD8) is conjugated to substrate proteins, was required for efficient HBV propagation. We also found that overexpression of sentrin-specific protease 8 (SENP8), which cleaves conjugated NEDD8, suppressed HBV propagation. Further, the catalytic activity of SENP8 was required for the suppression of HBV propagation. These results indicated that the reduction of neddylation negatively regulated HBV propagation. In addition, we demonstrated that suppression of HBV propagation via SENP8 overexpression was independent of hepatitis B protein X (HBx) and HBV promoter activity. Therefore, our data suggested that neddylation plays an important role in the late stages of HBV life cycles.