HBx targets centrosomal protein TAX1BP2 to promote genomic instability

Abstract

Centrosome is a major microtubule-organizing centre for regulating spindle assembly and bipolarity.Evidence suggests that cancer is a multi-step accumulation process of genomic instability resulted from centrosome dysfunction. One of the major forms of genomic instability is chromosomal instability, which is often presented as changes in chromosomal structure and number. Here we show that hepatitis B virus oncoprotein X protein (HBx), a pivotal factor in hepatocarcinogenesis, induces an increase in chromosome number and tumorigenicity. Microscopic observation illustrates that HBx expression results in centrosomal structure abnormality and multiple centrosomes. Molecular mechanism characterization suggests that HBx binds to a centrosome protein called TAX1BP2, which was previously shown to be an intrinsic block of centrosome over-duplication and a tumor suppressor in hepatocarcinogenesis. We further show that HBx down-regulates TAX1BP2 transcription by reducing its promoter activity. Taken together, our findings suggest a mechanism by which HBx results in hepatocarcinogenesis through centrosome dysfunction.