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Hepatitis B Virus X Protein Transcription Activation Domains Are Neither Required nor Sufficient for Cell Transformation¹

Institut für Molekularbiologie und Biochemie der Freien Universität Berlin, 14195 Berlin, Germany [K. G., A. G.]; Laboratory of Gene Expression, Fondazione A. Cesalpino, University of Rome "La Sapienza," 00161 Rome, Italy [S. P., M. L.]; and Department of Internal Medicine, Università di Cagliari, 09124 Cagliari, Italy [M. L.]

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.

¹ This work was supported by Grant GR. 384/13-2 from the Deutsche Forschungsgemeinschaft (to A. G.), Telethon A 64 (to M. L.), Associazione Italiana per la Ricerca sul Cancro (to M. L.), Consiglio Nazionale delle Ricerche-Applicazioni: Cliniche della Ricerca Oncologia (to M. L.), and by Grant PL96-3731 from the European Commission BIOMED 2 Programme.

² To whom requests for reprints should be addressed, at Institut für Molekularbiologie und Biochemie der Freien Universität Berlin, Arnimallee 22, 14195 Berlin, Germany, E-mail: graess@zedat.fu-berlin.de.

Received 6/25/98. Accepted 7/13/98.

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