Mitochondria ubiquitin ligase, MARCH5 resolves hepatitis B virus X protein aggregates in the liver pathogenesis.,Cell Death & Disease

当前位置： X-MOL 学术 › Cell Death Dis. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Mitochondria ubiquitin ligase, MARCH5 resolves hepatitis B virus X protein aggregates in the liver pathogenesis.
Cell Death & Disease ( IF 8.1 ) Pub Date : 2019-12-09 , DOI: 10.1038/s41419-019-2175-z
Young-Suk Yoo ₁ , Yeon-Ji Park _{1,

2} , Ho-Soo Lee ₁ , Nguyen Thi Kim Oanh ₁ , Mi-Young Cho ₁ , June Heo _{1,

2} , Eun-Seo Lee _{1,

2} , Hyeseon Cho ₃ , Yong-Yea Park ₄ , Hyeseong Cho _{1,

2}

Affiliation

Infection of hepatitis B virus (HBV) increase the incidence of chronic liver disease and hepatocellular carcinoma (HCC). The hepatitis B viral x (HBx) protein encoded by the HBV genome contributes to the pathogenesis of HCC and thus, negative regulation of HBx is beneficial for the alleviation of the disease pathogenesis. MARCH5 is a mitochondrial E3 ubiquitin ligase and here, we show that high MARCH5 expression levels are correlated with improved survival in HCC patients. MARCH5 interacts with HBx protein mainly accumulated in mitochondria and targets it for degradation. The N-terminal RING domain of MARCH5 was required for the interaction with HBx, and MARCH5H43W lacking E3 ligase activity failed to reduce HBx protein levels. High expression of HBx results in the formation of protein aggregates in semi-denaturing detergent agarose gels and MARCH5 mediates the elimination of protein aggregates through the proteasome pathway. HBx-induced ROS production, mitophagy, and cyclooxygenase-2 gene expression were suppressed in the presence of high MARCH5 expression. These results suggest MARCH5 as a target for alleviating HBV-mediated liver disease.

中文翻译：

线粒体泛素连接酶，MARCH5解决了肝脏发病机理中的乙型肝炎病毒X蛋白聚集体。

乙型肝炎病毒（HBV）的感染会增加慢性肝病和肝细胞癌（HCC）的发生率。HBV基因组编码的乙型肝炎病毒x（HBx）蛋白有助于HCC的发病机理，因此，对HBx的负调控有助于缓解疾病的发病机理。MARCH5是线粒体E3泛素连接酶，在这里，我们证明了高MARCH5表达水平与HCC患者的生存率提高相关。MARCH5与主要在线粒体中积累的HBx蛋白相互作用，并将其靶向降解。MARCH5的N端RING域是与HBx相互作用所必需的，而缺乏E3连接酶活性的MARCH5H43W无法降低HBx蛋白水平。HBx的高表达导致半变性洗涤剂琼脂糖凝胶中蛋白质聚集体的形成，而MARCH5介导通过蛋白酶体途径消除蛋白质聚集体。在高MARCH5表达的存在下，HBx诱导的ROS产生，线粒体和环氧合酶2基因表达受到抑制。这些结果表明，MARCH5是减轻HBV介导的肝病的靶标。

更新日期：2019-12-09

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11