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Function of Hepatitis B Virus X protein

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B型肝炎ウイルスX蛋白の機能

著者 村上 清史

著者別表示 Murakami Seishi

雑誌名 平成16(2004)年度 科学研究費補助金 特定領域研究 研究成果報告書概要

巻 2000   2004

ページ 4p.

発行年 2008‑05‑26

URL http://doi.org/10.24517/00066729

Creative Commons : 表示 ‑ 非営利 ‑ 改変禁止 http://creativecommons.org/licenses/by‑nc‑nd/3.0/deed.ja

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2004 Fiscal Year Final Research Report Summary

Function of Hepatitis B Virus X protein

Research Project

Project/Area Number

12213050

Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation Type

Single-year Grants

Review Section

Biological Sciences

Research Institution

KANAZAWA UNIVERSITY

Principal Investigator

MURAKAMI Seishi Dept of Mol. Oncology, Cancer Res. Inst., Professor, がん研究所, 教授 (90019878)

Co-Investigator(Kenkyū-buntansha)

HAYASHI Naoyuki Dept of Mol. Oncology, Cancer Res. Inst., Research Associate, がん研究所, 助⼿ (50253456)

Project Period (FY)

2000 – 2004

Keywords

HBv X protein / RNA polymerase / RPB5 / RMP / HBV replicon / Transcriptional modulation / Telomerase

Research Abstract

For better understanding molecular mechanism of transcriptional modulation by HBV X protein (HBx), we studied structure and function of RNA polymerase subunit 5 (RPB5) as a nuclear target of HBx, and contribution of HBx on immortalization and/or transformation process of human cells.

In addition, subcellular localization and nuclear function of RMP which is a functional antagonist of HBx. The followings are main results of the project in this fiscal year.

1) By analyzing clustered alanine substitution mutant (Cm) and point mutant (Pm) libraries of the middle part of RPB5, we pinpointed 6 resideus

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Research Products

(46 results)

All 2005 2004 2003 2002 2001 2000 All Journal Article (46 results) critical for HBx-binding and 6 residues for TFIIF subunit RAP30-binding.Among them, 4 residues・F76, 1104, T111 and S113, are critical both for the bindings. The former two residues are not solvent exposed and probably contributing to the structural integrity. T111 and S113 are exposed and is in near position to DNA in light of the Pol II crystal models. The 4 residues are also critical or impor tant for DNA-binding ability of RPB5 (in

preparation). Taken together, DNA-binding ability of RPB5 may be the target of HBx and RAP30.

2) Using the Cm library of HBx, we addressed the critical region(s) of HBx for augmentation ability on HBV replication in a HBV replicon system.

which is defective in X-ORF. Two discontinuous regions in the coactivation domain of HBx are indispensable for the augmentation effect on HBV replication. In the same experiment, the same regions were required not only for increase in HBV DNA but also for increase in pregenomic (pg) RNA.

The same regions were also critical for the coactivation function of HBx, suggesting that HBx coactivates pgRNA synthesis that resulted in increase in HBV DNA synthesis.

3) Recently it was found that RMP/URI, a functional antagonist of HBx, is localized with RPB5 in cytoplasm. Subcellular localization of RMP/URI can be modulated in the presence of DMAP1 and nuclear RMP/URI acts as a corepressor. From these results, RMP/URI is a regulatory protein in cytoplasm as well as nucleus.

4) We addressed whether HBx acts positively in immortalization and/or transformation process of human cells. In our preliminary results,

immortalization of human primary cells is barely affected by HBx, but transformation frequency of immortalized human cells seems to be augmented by HBx in the presence of activated oncogenes. This facilitating role of HBx requires the coactivation domain of HBx. Less

2005

[Journal Article] Transcriptional transactivation function of HBx protein is important for the augmentation role in Hepatitis B Virus replication 

2005

[Journal Article] Transcriptional transactivation function of HBx protein is important for the augmentation role in Hepatitis B Virus replication 

2004

[Journal Article] Subcellular localization of RPB5-mediating protein and its putative functional partner 

2004

[Journal Article] Hepatitis B virus X protein induces abgiogenesis by stabilizing hypoxia-Inducible factor-lalfa 

2004

[Journal Article] Effect of interaction between Hepatitis C Virus NS5A and NS5B on the Hepatitis C Virus replicon 

2004

[Journal Article] Mutational analysis of Hepatitis C Virus NS5B in the subgenomis replicon cell culture 

2004

[Journal Article] Nucleolin interacts with telomerase 

2004

[Journal Article] Hepatitis B virus X protein induces angiogenesis by stabilizing hypoxia-inducible factor-lalpha 

2004

[Journal Article] Subcellular localization of RPB5-mediating protein, RMP, and its putative functional partner 

2004

[Journal Article] Nucleolin interacts with telomerase 

2004

[Journal Article] Effect of interaction between Hepatitis C Virus NS5A and NS5B on the Hapatitis C Virus replicon 

2004

[Journal Article] Mutational analysis of Hepatitis C Virus NS5B in the sub -genomic replicon cell culture 

[Journal Article] Interaction with general transcription factor IIF(TFIIF) is required for the suppression of the activated transcription by RPB5-

2003

mediating protein RMP 

[Journal Article] Significant of immunological detection of human telomerase reverseranscriptase : re-evaluation of expression and localization of

2003

human telomerase reverse transcriptase 

2003

[Journal Article] Direct interaction between nucleolin and Hepatitis C Virus NS5B 

2003

[Journal Article] Telomerase maintains telomere structure in normal human cells 

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[Journal Article] Interaction with general transcription factor IIF(TFIIF) is required for the suppression of activated transcription by RPB5- mediating

2003

protein RMP. 

[Journal Article] Significance of immunological detection of human telomerase reverse transcriptase : re-evaluation of expression and localization of

2003

human telomarase reverse transcriptase 

2003

[Journal Article] Telomerase maintains telomere structure in normal human cells 

2003

[Journal Article] Direct interaction between Nucleoin and Hepatitis C Virus NS5B 

2002

[Journal Article] STM1, a gene which encodes a guanine quadruplex binding protein interacts with CDC13 in Saccharomycec cerevisiae 

[Journal Article] Two independent regions of human telomerase reverse transcriptase (hTERT) are important for their oligomerization and telomerase

2002

activity 

2002

[Journal Article] Hepatitis C Vims NS5A bind RNA-dependent RNA polymerase NS5B and modulates RdRP activity 

[Journal Article] Identification of serum anti-human telomerase reverse transcriptase (hTERT) auto-antibodies during progression to hepatocellular

2002

carcinoma 

2002

[Journal Article] Direct activation of telomerase by EGF through Est-madiated trans-activation of TERT via MAP kinase signaling pathway 

2002

[Journal Article] Oligomeric interaction of Hepatitis C Virus NS5B is critical for catalytic activity of RNA dependent RNA polymerase 

2002

[Journal Article] a gene which encodes a guanine quadruplex binding protein interacts with CDC13 in Saccharomycec cerevisiae 

[Journal Article] Two independent regions of human telomerase reverse transcriptase (hTERT) are important for their oligomerization and telomerase

2002

activity. 

[Journal Article] Identification of serum anti-human telomerase reverse transcriptase (hTERT) auto-antibodies during progression to hepatocellular

2002

carcinoma. 

2002

[Journal Article] Direct activation of telomerase by EGF through Ets-mediated transactivation of TERT via MAP kinase signaling pathway. 

2002

[Journal Article] Hepatitis C Virus NS5A Bind RNA-Dependent RNA polymerase NS5B and modulates RdRP activity. 

2002

[Journal Article] Oligomeric interaction of Hepatitis C Virus NS5B is critical for catalytic activity of RNA dependent RNA polymerase. 

2001

[Journal Article] Hepatitis B Virus X protein : A multifunctional regulatory protein 

[Journal Article] Direct interaction between the submit RAP30 of TFIIF and RNA polymerase subunit5(RPB5) which contributes to the association

2001

between TFIIF and RNA polymerase II 

2001

[Journal Article] Mutational analysis of the structure and functions of Hepatitis C Virus RNA-dependent RNA polymerase 

2001

[Journal Article] Hepatitis B Virus X protein : A multifunctional regulatory protein. 

[Journal Article] Direct interaction between the subunit RAP30 of TFIIF and RNA Polymerase subunit 5(RPB5) which contributes to the association

2001

between TFIIF and RNA polymerase II. 

2001

[Journal Article] Mutational analysis of the structure and functions of Hepatitis C Virus RNA-dependent RNA polymerase. 

2000

[Journal Article] Human Hepatitis B Virus X protein in a possible mediator of hypoxia Induced angiogenesis in hepatocellular carcinoma 

[Journal Article] Telomerase activity reconstituted in vitro with purified human telomerase reverse transcriptase and human telomerase RNA

2000

component 

2000

[Journal Article] A novel protein, RPM, which functionally counteracts 

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Published: 2008-05-26 URL: https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-12213050/122130502004kenkyu_seika_hokoku_

2000

[Journal Article] Expression and purification method of human telomarase reverse trans-criptase with Baculovirus expression system 

2000

[Journal Article] Human Hepatitis B Virus X protein is a possible Mediator of hypoxia induced angiogenesis in hepatocellular carcinoma. 

2000

[Journal Article] A novel protein, RMP, which functionally counteracts 

[Journal Article] Telomerase activity reconstituted in Vitro with purified human telomerase reverse transcriptase and human telomarase RNA

2000

component. 

2000

[Journal Article] Expression and purification method of human telomerase reverse transcriptase with Baculovirus expresssion system 

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