HEPATITIS-B VIRUS-X PROTEIN TRANSCRIPTION ACTIVATION DOMAINS ARE NEITHER REQUIRED NOR SUFFICIENT FOR CELL-TRANSFORMATION

The ability of the hepatitis B virus (HBV)-encoded X protein (HBx) to coactivate transcription of viral and cellular genes has been implicat ed in the development of HBV-related liver cancer. To dissect the tran sformation and the transcription activation properties of HBx, we gene rated REV2 cell lines expressing the wild-type and different truncated versions of the protein. Full-length HBx-expressing REV-2 cells displ ay an altered morphology and form large colonies in soft agar, A simil ar transformation efficiency has been obtained with a truncated versio n of HBx, which contains only the first 50 NH2-terminal amino acids (H Bx 1-50). in contrast, HBx mutants that lack the NH2-terminal segment but retain most of the transactivating function, as compared to the fu ll length HBx, were unable to alter the growth characteristic of REV-2 cells. Furthermore, abrogation of full-length HBx transcriptional act ivation by the insertion of two amino acids (Arg-Pro) at position 68 d id not affect REV-2 cells transformation. These results demonstrate th at the transactivation activity of HBx is neither essential nor suffic ient for tumor promotion.