Liver cancer (hepatocellular carcinoma, HCC) is one of the most prevalent cancer worldwide. Several etiological factors of HCC, including hepatitis B and C virus infection, liver cirrhosis and aflatoxin B1 intake has been identified. HBx, which is an oncogenic protein encoded by the hepatitis B virus, is strongly associated with hepatocarcinogenesis. Using stable HBx expressing cell, we showed that HBx induced chromosome gain, with amplification of numerical centrosomes and deregulation of centrosome ultrastructure. To dissect the mechanism for chromosome instability, our result revealed that HBx contributed to a hyperactive centrosome-microtubule dynamic by accelerating microtubule nucleation and polymerization. Further investigations suggested that HBx interacted with a centrosome linker protein TAX1BP2, which has previously been shown to function as an intrinsic block of centrosome amplification and a tumour suppressor in HCC. Restoring TAX1BP2 was able to block HBx-mediated centrosome amplification and abolish the HBx-mediated centrosome aberration, thereby suppressing chromosome instability. Thus, we demonstrate here a mechanism by which HBx deregulates centrosome-microtubule dynamics through interacting with TAX1BP2, which underlines the possibility of restoration of TAX1BP2 to rescue cells from chromosome instability.

肝癌（肝细胞癌，HCC）是世界上最流行的癌症之一。已经确定了肝癌的几个病因，包括乙型和丙型肝炎病毒感染，肝硬化和黄曲霉毒素B1摄入量。HBx是由乙型肝炎病毒编码的致癌蛋白，与肝癌发生密切相关。使用稳定的HBx表达细胞，我们发现HBx诱导了染色体的扩增，其中数字中心体的扩增和中心体超微结构的失控。为了剖析染色体不稳定性的机制，我们的结果表明，HBx通过加速微管成核和聚合作用而促进了高活性的中心体-微管动力学。进一步的研究表明HBx与中心体接头蛋白TAX1BP2相互作用，先前已显示它在肝癌中起着中心体放大的内在功能和抑癌作用。恢复TAX1BP2能够阻止HBx介导的中心体扩增，并消除HBx介导的中心体畸变，从而抑制染色体不稳定。因此，我们在这里证明了HBx通过与TAX1BP2相互作用来放松中心体-微管动力学的机制，这强调了恢复TAX1BP2来挽救染色体不稳定性的可能性。