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 implicated in the development of HBV-related liver cancer. To dissect the transformation and the transcription activation properties of HBx, we generated REV2 cell lines expressing the wild-type and different truncated versions of the protein. Full-length HBx-expressing REV-2 cells display an altered morphology and form large colonies in soft agar. A similar transformation efficiency has been obtained with a truncated version of HBx, which contains only the first 50 NH2-terminal amino acids (HBx 1-50). In contrast, HBx mutants that lack the NH2-terminal segment but retain most of the transactivating function, as compared to the full length HBx, were unable to alter the growth characteristic of REV-2 cells. Furthermore, abrogation of full-length HBx transcriptional activation by the insertion of two amino acids (Arg-Pro) at position 68 did not affect REV-2 cells transformation. These results demonstrate that the transactivation activity of HBx is neither essential nor sufficient for tumor promotion.
Institut für Molekularbiologie und Biochemie der Freien Universität Berlin, Germany.
K
K
Gottlob
S
S
Pagano
M
M
Levrero
A
A
Graessmann
D000957:Antigens, Viral, Tumor / Q000378:metabolism; D002472:Cell Transformation, Viral; D006515:Hepatitis B virus; D015534:Trans-Activators / Q000502:physiology*; D015533:Transcriptional Activation / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014764:Viral Proteins / Q000502:physiology*
D000957:Antigens, Viral, Tumor; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins