The hepatitis B virus (HBV) encodes a 16.5 kDa multifunctional protein termed pX or HBx, required for transcription of the viral genome and implicated in the development of hepatocellular carcinoma (HCC) in chronic HBV-infected patients. However, the mechanism of pX-mediated hepatocarcinogenesis remains unknown. pX is a multifunctional protein exhibiting a number of activities affecting transcription, cell growth, and apoptotic cell death. Although pX does not directly bind DNA, pX is regarded as a promiscuous transactivator, acting via a dual mechanism: in the cytoplasm, pX activates mitogenic signaling cascades; in the nucleus, pX interacts directly with members of the bZip class of transcription factors and with specific components of the basal transcriptional apparatus. The focus of this review is to describe the transactivation function of pX and its role in hepatocarcinogenesis.

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