乙型肝炎病毒X蛋白的研究进展_West China Medical Journal

Authors：

龚道银 ¹ , 陈恩强 ² , 朱柯霓 ³ , 张冬雪 ¹ , 俞尤嘉 ¹ ,  黄飞骏 ¹

Corresponding author：

黄飞骏, Email: daoyingong@163.com

Keywords：

X蛋白; 乙型肝炎病毒; 复制; 肝细胞癌

DOI：

10.7507/1002-0179.20130194

Video：

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乙型肝炎病毒(HBV)慢性持续感染与肝细胞癌（HCC）的发生密切相关。由HBV X基因编码的X蛋白（HBx）是一个多功能蛋白，可通过反式激活和蛋白相互作用持续调控病毒的生活周期和宿主细胞的代谢，最终导致肝细胞癌变。因此，近年来对于HBx在病毒复制和致HCC中的作用机制成为研究热点。

Citation： 龚道银,陈恩强,朱柯霓,张冬雪,俞尤嘉,黄飞骏. 乙型肝炎病毒X蛋白的研究进展. West China Medical Journal, 2013, 28(4): 609-613. doi: 10.7507/1002-0179.20130194 Copy

1.	Ng SA, Lee C. Hepatitis Bvirus X gene and hepatocarcinogenesis[J]. J Gastroenterol, 2011, 46(8): 974-990.
2.	Koike K. Hepatitis B virus X gene is implicated in liver carcinogenesis[J]. Cancer Lett, 2009, 286(1): 60-68.
3.	Neuveut C, Wei Y, Buendia MA. Mechanisms of HBV-related hepatocarcinogenesis[J]. J Hepatol, 2010, 52(4): 594-604.
4.	王月宾, 唐红. 乙型肝炎病毒X蛋白在HBV复制中作用的研究进展[J]. 华西医学, 2008, 23 (4): 917-918.
5.	Tang H, Oishin, Kanekos, et al. Molecular functions and biological roles of hepatitis B virus x protein[J]. Cancer Sci, 2006, 97(10): 977-983.
6.	Maria Stella De Mitri, Romina Cassini, Mauro Bernardi. Hepatitis Bvirus-related hepatocarcinogenesis: Molecular oncogenic potential of clear or occult infections[J]. Eur J Cancer, 2010, 46(12): 2178-2186.
7.	Chau DK f, Chen G G, Zhang H, et al. Differential Functions of C-and N-Terminal Hepatitis B x Protein in Liver Cells Treated with Doxorubicinin Normoxicor Hypoxic Condition[J]. PLoS ONE, 2012, 7(11): 50118.
8.	Bouchard MJ, Schneider RJ. The enigmatic X gene of hepatitis B virus[J]. J Virol, 2004, 78 (23): 12725 - 12734.
9.	Bouchard MJ, Navas-Martin S. Hepatitis B and C virus hepatocarcinogenesis: Lessons learned and future challenges[J]. Cancer Lett, 2011, 305(2): 123-143.
10.	Tang H, Delgermaa L, Huang FJ, et al. The transcriptional transactivation function of HBx protein is important for its augmentation role in hepatitis B virus replication[J]. J Virol, 2005, 79(9): 5548-5556.
11.	MAA van de Klundert, FJ. vanHemert, HL Zaaijer. The Hepatitis B virus X protein inhibits thymine DNA glycosylase initiated base excision repair[J]. Plos One, 2012, 7(11): 48940.
12.	Rawat S, Clippinger AJ, Bouchard MJ. Modulation of Apoptotic Signaling by the Hepatitis B Virus X Protein[J]. Viruses, 2012, 4: 2945-2972.
13.	Zhang Tao, Zhang Jp, You Xn, et al. Hepatitis B virus x protein modulates oncogene yes-associated protein by CREB to promote growth of hepatoma cells[J]. Hepatology, 2012, 56(6): 2051- 2059.
14.	Du Y, Kong G, You X, et al. Elevation of highly up-regulated in liver cancer (HULC) by hepatitis B virus X protein promotes hepatoma cell proliferation via down-regulating p18[J]. J Biol Chem, 2012, 287(31): 26302-26311.
15.	Clippinger AJ, Bouchard MJ. Hepatitis B virus HBx protein localizes to mitochondria in primary rat hepatocytes and modulates mitochondrial membrane potential[J]. J Virol, 2008, 82(14): 6798-6811.
16.	Knoll S, Fürst K, Thomas S, et al. Dissection of cell context-dependent interactions between HBx and p53 family members in regulation of apoptosis: a role for HBV-induced HCC[J]. Cell Cycle, 2011, 10(20): 3554-3565.
17.	Gearhart TL, Bouchard MJ. The hepatitis B virus X protein modulates hepatocyte proliferation pathways to stimulate viral replication[J]. J Virol, 2010, 84(6): 2675-2686.
18.	Wang Fan, Xia XM, Wang JL, et al. Notch1 signaling contributes to the oncogenic effect of HBx on human hepatic cells[J]. Biotechnol Lett, 2013, 35(1): 29-37.
19.	TM Bui-Nguyen, SB Pakala, RD Sirigiri.NF-κB signaling mediates the induction of MTA1 by hepatitis B virus transactivator protein HBx[J]. Oncogene, 2010, 29(8): 1179-1189.
20.	Zhang ZS, Sun E, James JH, et al. Inhibition of Cellular Proteasome activities mediates HBx-independent hepatitis B virus replication in vivo[J]. J Virol, 2010, 84(18): 9326-9331.
21.	S Kim, S-Y Park, H Yong, et al. HBV X protein targets hBubR1, which induces dysregulation of the mitotic Checkpoint[J]. Oncogene, 2008, 27(24): 3457-3464.
22.	Wei W, Huang W, Pan Y, et al. Functional switch of viral protein HBx on cell apoptosis, transformation, and tumorigenesis in association with oncoprotein Ras[J]. Cancer Lett, 2006, 244(1): 119-128.
23.	Belloni L, Pollici no T, De Nicola F, et al. Nuclear HBx binds the HBV mini chromosome and modifies the epigenetic regulation of cccDNA function[J]. Proc Natl Acad Sci USA, 2009, 106(47): 19975 -19979.
24.	Liu H, Xu L, He H, et al. Hepatitis B virus X protein promotes hepatoma cell invasion and metastasis by stabilizing Snail protein[J]. Cancer Sci, 2012, 103(12): 2072-2081.
25.	Ye Jin Kim, Jin Kyu Jung, Sun Young Lee, et al. Hepatitis B virus X protein overcomes stress-induced premature senescence by repressing p16INK4α expression via DNA methylation[J]. Cancer Lett, 2010, 288(2): 226-235.
26.	Michael C Kew. Hepatitis B virus x protein in the pathogenesis of hepatitis B virus-induced hepatocellular carcinoma[J]. J Gastroen Hepatol, 2011, 26 (Suppl 1): 144-152.
27.	Wen W, Ding J, Sun W, et al. Cyclin G1-mediated epithelial-mesenchymal transition via phosphoinositide 3-kinase/Akt signaling facilitates liver cancer progression[J]. Hepatology, 2012, 55(6): 1787-1798.
28.	Wei Xf, Xiang TX, Ren GS, et al. miR-101 is sdown-regulated by the hepatitis B virus x protein and induces aberrant DNA methylation by targeting DNA methyltransferase 3A[J]. Cell Signal, 2013, 25(2): 439-446.
29.	Wang Peng, Guo QS, Wang ZW, et al. HBx induces HepG-2 cells autophagy through PI3K/Akt-mTOR pathway[J]. Mol Cell Biochem, 2013, 372(1-2): 161-168.

1. 　Ng SA, Lee C. Hepatitis Bvirus X gene and hepatocarcinogenesis[J]. J Gastroenterol, 2011, 46(8): 974-990.
2. 　Koike K. Hepatitis B virus X gene is implicated in liver carcinogenesis[J]. Cancer Lett, 2009, 286(1): 60-68.
3. 　Neuveut C, Wei Y, Buendia MA. Mechanisms of HBV-related hepatocarcinogenesis[J]. J Hepatol, 2010, 52(4): 594-604.
4. 　王月宾, 唐红. 乙型肝炎病毒X蛋白在HBV复制中作用的研究进展[J]. 华西医学, 2008, 23 (4): 917-918.
5. 　Tang H, Oishin, Kanekos, et al. Molecular functions and biological roles of hepatitis B virus x protein[J]. Cancer Sci, 2006, 97(10): 977-983.
6. 　Maria Stella De Mitri, Romina Cassini, Mauro Bernardi. Hepatitis Bvirus-related hepatocarcinogenesis: Molecular oncogenic potential of clear or occult infections[J]. Eur J Cancer, 2010, 46(12): 2178-2186.
7. 　Chau DK f, Chen G G, Zhang H, et al. Differential Functions of C-and N-Terminal Hepatitis B x Protein in Liver Cells Treated with Doxorubicinin Normoxicor Hypoxic Condition[J]. PLoS ONE, 2012, 7(11): 50118.
8. 　Bouchard MJ, Schneider RJ. The enigmatic X gene of hepatitis B virus[J]. J Virol, 2004, 78 (23): 12725 - 12734.
9. 　Bouchard MJ, Navas-Martin S. Hepatitis B and C virus hepatocarcinogenesis: Lessons learned and future challenges[J]. Cancer Lett, 2011, 305(2): 123-143.
10. 　Tang H, Delgermaa L, Huang FJ, et al. The transcriptional transactivation function of HBx protein is important for its augmentation role in hepatitis B virus replication[J]. J Virol, 2005, 79(9): 5548-5556.
11. 　MAA van de Klundert, FJ. vanHemert, HL Zaaijer. The Hepatitis B virus X protein inhibits thymine DNA glycosylase initiated base excision repair[J]. Plos One, 2012, 7(11): 48940.
12. 　Rawat S, Clippinger AJ, Bouchard MJ. Modulation of Apoptotic Signaling by the Hepatitis B Virus X Protein[J]. Viruses, 2012, 4: 2945-2972.
13. 　Zhang Tao, Zhang Jp, You Xn, et al. Hepatitis B virus x protein modulates oncogene yes-associated protein by CREB to promote growth of hepatoma cells[J]. Hepatology, 2012, 56(6): 2051- 2059.
14. 　Du Y, Kong G, You X, et al. Elevation of highly up-regulated in liver cancer (HULC) by hepatitis B virus X protein promotes hepatoma cell proliferation via down-regulating p18[J]. J Biol Chem, 2012, 287(31): 26302-26311.
15. 　Clippinger AJ, Bouchard MJ. Hepatitis B virus HBx protein localizes to mitochondria in primary rat hepatocytes and modulates mitochondrial membrane potential[J]. J Virol, 2008, 82(14): 6798-6811.
16. 　Knoll S, Fürst K, Thomas S, et al. Dissection of cell context-dependent interactions between HBx and p53 family members in regulation of apoptosis: a role for HBV-induced HCC[J]. Cell Cycle, 2011, 10(20): 3554-3565.
17. 　Gearhart TL, Bouchard MJ. The hepatitis B virus X protein modulates hepatocyte proliferation pathways to stimulate viral replication[J]. J Virol, 2010, 84(6): 2675-2686.
18. 　Wang Fan, Xia XM, Wang JL, et al. Notch1 signaling contributes to the oncogenic effect of HBx on human hepatic cells[J]. Biotechnol Lett, 2013, 35(1): 29-37.
19. 　TM Bui-Nguyen, SB Pakala, RD Sirigiri.NF-κB signaling mediates the induction of MTA1 by hepatitis B virus transactivator protein HBx[J]. Oncogene, 2010, 29(8): 1179-1189.
20. 　Zhang ZS, Sun E, James JH, et al. Inhibition of Cellular Proteasome activities mediates HBx-independent hepatitis B virus replication in vivo[J]. J Virol, 2010, 84(18): 9326-9331.
21. 　S Kim, S-Y Park, H Yong, et al. HBV X protein targets hBubR1, which induces dysregulation of the mitotic Checkpoint[J]. Oncogene, 2008, 27(24): 3457-3464.
22. 　Wei W, Huang W, Pan Y, et al. Functional switch of viral protein HBx on cell apoptosis, transformation, and tumorigenesis in association with oncoprotein Ras[J]. Cancer Lett, 2006, 244(1): 119-128.
23. 　Belloni L, Pollici no T, De Nicola F, et al. Nuclear HBx binds the HBV mini chromosome and modifies the epigenetic regulation of cccDNA function[J]. Proc Natl Acad Sci USA, 2009, 106(47): 19975 -19979.
24. 　Liu H, Xu L, He H, et al. Hepatitis B virus X protein promotes hepatoma cell invasion and metastasis by stabilizing Snail protein[J]. Cancer Sci, 2012, 103(12): 2072-2081.
25. 　Ye Jin Kim, Jin Kyu Jung, Sun Young Lee, et al. Hepatitis B virus X protein overcomes stress-induced premature senescence by repressing p16INK4α expression via DNA methylation[J]. Cancer Lett, 2010, 288(2): 226-235.
26. 　Michael C Kew. Hepatitis B virus x protein in the pathogenesis of hepatitis B virus-induced hepatocellular carcinoma[J]. J Gastroen Hepatol, 2011, 26 (Suppl 1): 144-152.
27. 　Wen W, Ding J, Sun W, et al. Cyclin G1-mediated epithelial-mesenchymal transition via phosphoinositide 3-kinase/Akt signaling facilitates liver cancer progression[J]. Hepatology, 2012, 55(6): 1787-1798.
28. 　Wei Xf, Xiang TX, Ren GS, et al. miR-101 is sdown-regulated by the hepatitis B virus x protein and induces aberrant DNA methylation by targeting DNA methyltransferase 3A[J]. Cell Signal, 2013, 25(2): 439-446.
29. 　Wang Peng, Guo QS, Wang ZW, et al. HBx induces HepG-2 cells autophagy through PI3K/Akt-mTOR pathway[J]. Mol Cell Biochem, 2013, 372(1-2): 161-168.

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