Turnover of hepatitis B virus X protein is regulated by damaged DNA-binding complex
Turnover of hepatitis B virus X protein is regulated by damaged DNA-binding complex
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DOI：
10.1128/jvi.76.13.6495-6501.2002
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发表时间：
2002-07-01
影响因子：
5.4
通讯作者：
Transy, C
中科院分区：
文献类型：
--
作者：
Bergametti, F;Sitterlin, D;Transy, C
哺乳动物B型肝炎病毒编码一种必需的调节蛋白，称为X，其也可能与慢性感染相关的肝癌发展有关。X蛋白，在人类病毒中也被称为HBx，在土拨鼠病毒中也被称为WHx，已被报道与许多细胞蛋白结合，包括受损DNA结合（DDB）复合物的DDB 1亚基。我们以前的工作提供了遗传证据VMx-DDB 1相互作用的重要性，在活动的X蛋白和建立病毒感染土拨鼠。在本研究中，DDB 1对X蛋白的直接作用被记录。两种蛋白质之间的物理相互作用导致X蛋白质稳定性的增加。这种作用是由于保护病毒蛋白免受蛋白酶体介导的降解。在DDB异二聚体的第二亚基DDB 2存在下，WHx的保护被克服。与HBx报告的观察结果一致，发现DDB 2直接结合WHx。然而，DDB 2对X稳定化的抵消作用需要DDB 2-DDB 1相互作用。总之，这些发现证实了X蛋白和DDB 1-DDB 2异源二聚体之间的物理和功能联系，导致病毒蛋白库的调节。
Mammalian hepatitis B viruses encode an essential regulatory protein, termed X, which may also be implicated in liver cancer development associated with chronic infection. X protein, also referred to as HBx in human virus and WHx in woodchuck virus, has been reported to bind to a number of cellular proteins, including the DDB1 subunit of the damaged DNA-binding (DDB) complex. Our previous work provided genetic evidence for the importance of VMx-DDB1 interaction in both the activity of the X protein and establishment of viral infection in woodchucks. In the present study, a direct action of DDB1 on the X protein is documented. Physical interaction between the two proteins leads to an increase in X protein stability. This effect results from protection of the viral protein from proteasome-mediated degradation. Protection of WHx is overcome in the presence DDB2, the second subunit of the DDB heterodimer. In keeping with observations reported for HBx, DDB2 was found to directly bind to WHx. Nonetheless, the counteracting effect of DDB2 on X stabilization requires DDB2-DDB1 interaction. Taken together, these findings substantiate the physical and functional connection between the X protein and the DDB1-DDB2 heterodimer, leading to the regulation of the pool of the viral protein.