This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gottlob, K. Articles by Graessmann, A. Search for Related Content PubMed PubMed Citation Articles by Gottlob, K. Articles by Graessmann, A.

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.

This article has been cited by other articles:

				X. Liu, L. Wang, S. Zhang, J. Lin, S. Zhang, M. A. Feitelson, H. Gao, and M. Zhu Mutations in the C-terminus of the X protein of hepatitis B virus regulate Wnt-5a expression in hepatoma Huh7 cells: cDNA microarray and proteomic analyses Carcinogenesis, June 1, 2008; 29(6): 1207 - 1214. [Abstract] [Full Text] [PDF]

				Y.-G. Yoo and M.-O. Lee Hepatitis B Virus X Protein Induces Expression of Fas Ligand Gene through Enhancing Transcriptional Activity of Early Growth Response Factor J. Biol. Chem., August 27, 2004; 279(35): 36242 - 36249. [Abstract] [Full Text] [PDF]

				R. Nijhara, S. S. Jana, S. K. Goswami, A. Rana, S. S. Majumdar, V. Kumar, and D. P. Sarkar Sustained Activation of Mitogen-Activated Protein Kinases and Activator Protein 1 by the Hepatitis B Virus X Protein in Mouse Hepatocytes In Vivo J. Virol., November 1, 2001; 75(21): 10348 - 10358. [Abstract] [Full Text] [PDF]

				H. Tu, C. Bonura, C. Giannini, H. Mouly, P. Soussan, M. Kew, P. Paterlini-Brechot, C. Brechot, and D. Kremsdorf Biological Impact of Natural COOH-Terminal Deletions of Hepatitis B Virus X Protein in Hepatocellular Carcinoma Tissues Cancer Res., November 1, 2001; 61(21): 7803 - 7810. [Abstract] [Full Text] [PDF]

				S.-F. Chang, H. J. Netter, E. Hildt, R. Schuster, S. Schaefer, Y.-C. Hsu, A. Rang, and H. Will Duck Hepatitis B Virus Expresses a Regulatory HBx-Like Protein from a Hidden Open Reading Frame J. Virol., January 1, 2001; 75(1): 161 - 170. [Abstract] [Full Text]

				R. Weil, H. Sirma, C. Giannini, D. Kremsdorf, C. Bessia, C. Dargemont, C. Brechot, and A. Israel Direct Association and Nuclear Import of the Hepatitis B Virus X Protein with the NF-kappa B Inhibitor Ikappa Balpha Mol. Cell. Biol., September 1, 1999; 19(9): 6345 - 6354. [Abstract] [Full Text] [PDF]

				K. Gottlob, M. Fulco, M. Levrero, and A. Graessmann The Hepatitis B Virus HBx Protein Inhibits Caspase 3 Activity J. Biol. Chem., December 11, 1998; 273(50): 33347 - 33353. [Abstract] [Full Text] [PDF]

				W.-L. Shih, M.-L. Kuo, S.-E. Chuang, A.-L. Cheng, and S.-L. Doong Hepatitis B Virus X Protein Inhibits Transforming Growth Factor-beta -induced Apoptosis through the Activation of Phosphatidylinositol 3-Kinase Pathway J. Biol. Chem., August 11, 2000; 275(33): 25858 - 25864. [Abstract] [Full Text] [PDF]

				J. Diao, A. A. Khine, F. Sarangi, E. Hsu, C. Iorio, L. A. Tibbles, J. R. Woodgett, J. Penninger, and C. D. Richardson X Protein of Hepatitis B Virus Inhibits Fas-mediated Apoptosis and Is Associated with Up-regulation of the SAPK/JNK Pathway J. Biol. Chem., March 9, 2001; 276(11): 8328 - 8340. [Abstract] [Full Text] [PDF]

				I. Jaitovich-Groisman, N. Benlimame, B. L. Slagle, M. H. Perez, L. Alpert, D. J. Song, N. Fotouhi-Ardakani, J. Galipeau, and M. A. Alaoui-Jamali Transcriptional Regulation of the TFIIH Transcription Repair Components XPB and XPD by the Hepatitis B Virus x Protein in Liver Cells and Transgenic Liver Tissue J. Biol. Chem., April 20, 2001; 276(17): 14124 - 14132. [Abstract] [Full Text] [PDF]

				C. Tarn, S. Lee, Y. Hu, C. Ashendel, and O. M. Andrisani Hepatitis B Virus X Protein Differentially Activates RAS-RAF-MAPK and JNK Pathways in X-transforming Versus Non-transforming AML12 Hepatocytes J. Biol. Chem., September 7, 2001; 276(37): 34671 - 34680. [Abstract] [Full Text] [PDF]