Molecular functions and biological roles of hepatitis B virus x protein

Cancer Science

Volumn 97, Issue 10, 2006, Pages 977-983

  Tang, Hong ^a,b,c   Oishi, Naoki ^c   Kaneko, Shuichi ^c   Murakami, Seishi ^a,b  

^a BEIJING UNIVERSITY OF POSTS AND TELECOMMUNICATIONS   (China)

^b SICHUAN UNIVERSITY   (China)

^c KANAZAWA UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

HEPATITIS B VIRUS X PROTEIN; RAS PROTEIN;

APOPTOSIS; CELL CYCLE; GENETIC STABILITY; HEPATITIS B; HEPATITIS B VIRUS; HUMAN; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; MOLECULAR DYNAMICS; NONHUMAN; ONCOGENE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; REPLICON; REVIEW; SENESCENCE; SIGNAL TRANSDUCTION; VIRUS CELL TRANSFORMATION; VIRUS REPLICATION; VIRUS TRANSCRIPTION;

AMINO ACID SEQUENCE; CARCINOMA, HEPATOCELLULAR; CELL TRANSFORMATION, VIRAL; HEPATITIS B VIRUS; HUMANS; LIVER NEOPLASMS; MOLECULAR SEQUENCE DATA; TRANS-ACTIVATORS; VIRUS REPLICATION;

EID: 33748288087     PISSN: 13479032     EISSN: 13497006     Source Type: Journal    
DOI: 10.1111/j.1349-7006.2006.00299.x     Document Type: Review

References (72)

1. Arbuthnot P, Kew M. Hepatitis B virus and hepatocellular carcinoma. Int J Exp Pathol 2001; 82: 77-100.
2. Murakami S. Hepatitis B Virus X protein: Structure, function biology. Intervirol 1999; 42: 82-99.
3. Murakami S. Hepatitis B Virus X protein: A multifunctional regulatory protein. J Gastroenterol 2001; 36: 651-60.
4. Kajino K, Aoki H, Hino O. Genomic instability involved in virus-related hepatocarcinogenesis. Intervirol 1995; 38: 170-2.
5. Chisari FV. Hepatitis B virus transgenic mice: Models of viral immunobiology and pathogenesis. Curr Top Microbiol Immunol 1996; 206: 149-73.
6. Araki K, Miyazaki J, Yamamura K et al. Expression and replication of hepatitis B virus genome in transgenic mice. Proc Natl Acad Sci USA 1989; 86: 207-11.
7. Seeger C, Mason WS. Hepatitis B virus biology. Microbiol Mol Biol Rev 2000; 64: 51-68.
8. Yen TSB. Regulation of hepatitis B virus gene expression. Semin Virol 1993; 4: 33-42.
9. Doitsh G. Enhancer I predominance in hepatitis B virus gene expression. Mol Cell Biol 2004; 24: 1799-808.
10. Nassal M, Schaller H. Hepatitis B virus replication. Trends Microbiol 1993; 1: 221-8.
11. Murakami S, Cheong JH, Kaneko S et al. Transactivation of human hepatitis B virus X protein, HBx operates through a mechanism distinct from protein kinase C and okadaic acid activation pathways. Virol 1994; 199: 243-6.
12. Murakami S, Cheong JH, Kaneko S et al. Autoregulation of human hepatitis B virus X gene. In: Nishioka, K, Suzuki, H, Mishiro, S, Oda, T, eds. Viral Hepatitis and Liver Diseases. Tokyo: Springer Verlauf, 1994; 743-7.
13. Dandri M, Schirmacher P, Rogler CE et al. Woodchuck hepatitis virus X protein is present in chronically infected woodchuck liver and woodchuck hepatocellular carcinomas which are permissive for viral replication. J Virol 1996; 70: 5246-54.
14. Dandri M, Petersen J, Rogler CE et al. Metabolic labeling of woodchuck hepatitis B virus X protein in naturally infected hepatocytes reveals a bimodal half-life and association with the nuclear framework. J Virol 1998; 72: 9359-64.
15. Nomura T, Lin Y, Murakami S et al. Human Hepatitis B virus X protein is detectable in nuclei of transfected cells, and active for transactivation. Biochim Biophys Acta 1999; 1453: 330-40.
16. Forgues M, Marrogi AJ, Wang XW et al. Interaction of the hepatitis B virus X protein with the Crm1-dependent nuclear export pathway. J Biol Chem 2001; 276: 22.797-803.
17. Forgues M, Difilippantonio MJ, Wang XW et al. Involvement of Crm1 in hepatitis B virus X protein-induced aberrant centriole replication and abnormal mitotic spindles. Mol Cell Biol 2003; 23: 5282-92.
18. Elmore LW, Hancock AR, Harris CC et al. Hepatitis B virus X protein and p53 tumor suppressor interactions in the modulation of apoptosis. Proc Natl Acad Sci USA 1997; 94: 14.707-12.
19. Lin Y, Nomura T, Murakami S et al. The transactivation and p53-interaction functions of HBx are mutually interfering but distinct. Cancer Res 1997; 57: 5137-42.
20. Lee DK, Park SH, Kim SJ et al. The hepatitis B virus encoded oncoprotein pX amplifies TGF-beta family signaling through direct interaction with Smad4: Potential mechanism of hepatitis B virus-induced liver fibrosis. Genes Dev 2001; 15: 455-66.
21. Andrisani OM, Barnabas S. The transcriptional function of the hepatitis B virus X protein and its role in hepatocarcinogenesis. Int J Oncol 1999; 15: 373-9.
22. Cross JC, Wen P, Rutter WJ et al. Transactivation by hepatitis B virus X protein is promiscuous and dependent on mitogen-activated cellular serine/threonine kinases. Proc Natl Acad Sci USA 1993; 90: 8078-82.
23. Cheong JH, Yi MK, Murakami S et al. Human RPB5, a subunit shared by eukaryotic nuclear polymerases, binds human hepatitis B virus X protein and may play a role in X transactivation. EMBO J 1995; 14: 143-50.
24. Lin Y, Reoder RG, Murakami S et al. The HBV X protein is a co-activator of activated transcription that modulates the transcription machinery and distal binding activators. J Biol Chem 1998; 273: 27.097-103.
25. Haviv I, Vaizel D, Shaul Y. pX, the HBV-encoded coactivator, interacts with components of the transcription machinery and stimulates transcription in a TAF-independent manner. EMBO J 1996; 15: 3413-20.
26. Murakami S, Cheong JH, Kaneko S et al. Human hepatitis B virus X gene encodes a regulatory domain which represses transactivation of X protein. J Biol Chem 1994; 269: 15.118-23.
27. Tang H, Delgermaa L, Murakami S et al. The transcriptional transactivation function of HBx protein is important for its augmentation role in hepatitis B virus replication. J Virol 2005; 79: 5548-56.
28. Le TTT, Zhang S, Murakami S et al. Mutational analysis of human RNA polymerase II subunit 5 (RPB5): The residues critical for interactions with TFIIF subunit RAP30 and Hepatitis B Virus X protein. J Biochem (Tokyo) 2005; 138: 215-24.
29. Doitsh G, Shaul Y. HBV transcription repression in response to genotoxic stress is p53-dependent and abrogated by pX. Oncogene 1999; 18: 7506-13.
30. Ahn JY, Chung EY, Jang KL et al. Transcriptional repression of p21 (waf1) promoter by hepatitis B virus X protein via a p53-independent pathway. Gene 2001; 275: 163-8.
31. Zhang Z, Torii N, Liang TJ et al. Structural and functional characterization of interaction between hepatitis B virus X protein and the proteasome complex. J Biol Chem 2000; 275: 15157-65.
32. Zhang Z, Protzer U, Liang J et al. Inhibition of cellular proteasome activities enhances hepadnavirus replication in an HBX-dependent manner. J Virol 2004; 78: 4566-72.
33. Lee TH, Elledge SJ, Butel JS. Hepatitis B virus X protein interacts with a probable cellular DNA repair protein. J Virol 1995; 69: 1107-14.
34. Jia L, Wang XW, Harris CC. Hepatitis B virus X protein inhibits nucleotide excision repair. Int J Cancer 1999; 80: 875-79.
35. Klein NP, Schneider RJ. Activation of Src family kinases by hepatitis B virus HBx protein and coupled signaling to Ras. Mol Cell Biol 1997; 17: 6427-36.
36. Bouchard MJ, Wang LH, Schneider RJ et al. Calcium signaling by HBx protein in hepatitis B virus DNA replication. Science 2001; 294: 2376-8.
37. Bouchard MJ, Wang L, Schneider RJ. Activation of focal adhesion kinase by hepatitis B virus HBx protein: Multiple functions in viral replication. J Virol 2006; 80: 4406-14.
38. Takada S, Shirakata Y, Koike K et al. Association of hepatitis B virus X protein with mitochondria causes mitochondrial aggregation at the nuclear periphery, leading to cell death. Oncogene 1999; 18: 6965-73.
39. Huh KW, Siddiqui A. Characterization of the mitochondrial association of hepatitis B virus X protein, HBx. Mitochondrion 2002; 1: 349-59.
40. Tanaka Y, Kanai F, Omata M et al. Interaction of the hepatitis B virus X protein (HBx) with heat shock protein 60 enhances HBx-mediated apoptosis. Biochem Biophys Res Commun 2004; 318: 461-9.
41. Zhang SM, Sun DC, Wang SQ et al. HBx protein of hepatitis B virus (HBV) can form complex with mitochondrial HSP60 and HSP70. Arch Virol 2005; 150: 1579-90.
42. Blum HE, Zhang ZS, Wands JR. Hepatitis B virus X protein is not central to the viral life cycle in vitro. J Virol 1992; 66: 1223-7.
43. Chen HS, Kaneko S, Miller RH et al. The woodchuck hepatitis virus X gene is important for establishment of virus infection in woodchucks. J Virol 1993; 67: 1218-26.
44. Zoulim F, Saputelli J, Seeger C. Woodchuck hepatitis virus X protein is required for viral infection in vivo. J Virol 1994; 68: 2026-30.
45. Zheng Y, Johnson DL, Ou JH. Regulation of hepatitis B virus replication by the ras-mitogen-activated protein kinase signaling pathway. J Virol 2003; 77: 7707-12.
46. Xu Z, Yen TS, Ou JH et al. Enhancement of hepatitis B virus replication by its X protein in transgenic mice. J Virol 2002; 76: 2579-84.
47. Bouchard MJ, Puro RJ, Schneider RJ et al. Activation and inhibition of cellular calcium and tyrosine kinase signaling pathways identify targets of the HBx protein involved in hepatitis B virus replication. J Virol 2003; 77: 7713-9.
48. Melegari M, Wolf SK, Schneider RJ. Hepatitis B virus DNA replication is coordinated by core protein serine phosphorylation and HBx expression. J Virol 2005; 79: 9810-20.
49. Leupin O, Bontron S, Strubin M et al. Hepatitis B virus X protein stimulates viral genome replication via a DDB1-dependentpathway distinct from that leading to cell death. J Virol 2005; 79: 4238-45.
50. Kim CM, Koike K, Jay G et al. HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature 1991; 351: 317-20.
51. Lee TH, Finegold MJ, Butel JS et al. Hepatitis B virus transactivator X protein is not tumorigenic in transgenic mice. J Virol 1990; 64: 5939-47.
52. Terradillos O, Billet O, Buendia MA et al. The hepatitis B virus X gene potentiates c-myc-induced liver oncogenesis in transgenic mice. Oncogene 1997; 14: 395-404.
53. Reifenberg K, Lohler J, Schlicht HJ et al. Long-term expression of the hepatitis B virus core-e- and X-proteins does not cause pathologic changes in transgenic mice. J Hepatol 1997; 26: 119-30.
54. Hu Z, Zhang Z, Liang TJ et al. Altered proteolysis and global gene expression in hepatitis B virus X transgenic mouse liver. J Virol 2006; 80: 1405-13.
55. Yul DY, Murakami S, Lee KK et al. Incidence of hepatocellular carcinoma in the transgenic mice expressing hepatitis B virus X-protein. J Hepatol 1999; 31: 123-32.
56. Madden CR, Finegold MJ, Slagle BL. Hepatitis B virus X protein acts as a tumor promoter in development of diethylnitrosamine-induced preneoplastic lesions. J Virol 2001; 75: 3851-8.
57. Shirakata Y, Kawada M, Koike K et al. The X gene of hepatitis B virus induced growth stimulation and tumorigenic transformation of mouse NIH3T3 cells. Jpn J Cancer Res 1989; 80: 617-21.
58. Oguey D, Dumenco LL, Fausto N et al. Analysis of the tumorigenicity of the X gene of hepatitis B virus in a nontransformed hepatocyte cell line and the effects of cotransfection with a murine p53 mutant equivalent to human codon 249. Hepatology 1996; 24: 1024-33.
59. Seifer M, Gerlich WH. Increased growth of permanent mouse fibroblasts in soft agar after transfection with hepatitis B virus DNA. Arch Virol 1992; 126: 119-28.
60. Seifer M, Hohne M, Gerlich WH et al. In vitro tumorigenicity of hepatitis B virus DNA and HBx protein. J Hepatol 1991; 13 (Suppl 4): S61-5.
61. Schuster R, Gerlich WH, Schaefer S. Induction of apoptosis by the transactivating domains of the hepatitis B virus X gene leads to suppression of oncogenic transformation of primary rat embryo fibroblasts. Oncogene 2000; 19: 1173-80.
62. Schuster R, Hildt E, Schaefer S et al. Conserved transactivating and pro-apoptotic functions of hepadnaviral X protein in ortho- and avihepadnaviruses. Oncogene 2002; 21: 6606-13.
63. Kim YC, Song KS, Ryu WS et al. Activated ras oncogene collaborates with HBx gene of hepatitis B virus to transform cells by suppressing HBx-mediated apoptosis. Oncogene 2001; 20: 16-23.
64. Artandi SE, DePinho RA. Mice without telomerase: What can they teach us about human cancer? Nat Med 2000; 6: 852-5.
65. Sharpless NE, DePinho RA. Cancer: Crime and punishment. Nature 2005; 436: 636-7.
66. Braig M, Lee S, Schmitt CA et al. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 2005; 436: 636-7.
67. Shlomai A, Shaul Y. Inhibition of hepatitis B virus expression and replication by RNA interference. Hepatology 2003; 37: 764-70.
68. Hamasaki K, Nakao K, Eguchi K et al. Short interfering RNA-directed inhibition of hepatitis B virus replication. FEBS Lett 2003; 543: 51-4.
69. Chan DW, Ng IO. Knock-down of hepatitis B virus X protein reduces the tumorigenicity of hepatocellular carcinoma cells. J Pathol 2006; 208: 372-80.
70. Kalra N, Kumar V. The X protein of hepatitis B virus binds to the F box protein Skp2 and inhibits the ubiquitination and proteasomal degradation of c-Myc. FEBS Lett 2006; G580: 431-6.
71. Rui E, Moura PR, Kobarg J et al. Interaction of the hepatitis B virus protein HBx with the human transcription regulatory protein p120E4F in vitro. Virus Res 2006; 115: 31-42.
72. Kim KH, Seong BL. Pro-apoptotic function of HBV X protein is mediated by interaction with c-FLIP and enhancement of death-inducing signal. EMBO J 2003; 22: 2104-16.