| Project/Area Number |
09044278
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Molecular biology
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| Research Institution | Kanazawa University |
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Principal Investigator |
MURAKAMI Seishi Kanazawa Univ., Cancer Research Inst.Prof., がん研究所, 教授 (90019878)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Naoyuki , 助手 (50253456)
NOMURA Takahiro , 助手 (80115261)
ROEDER Robert Rockefeller Univ.Lab.Biochem.& Mol.Biol., Prof, 教授
ROEDER Robet ロックフェラー大学, 教授
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1998: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1997: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Keywords | Transcription / Hepatitis B Virus / X protein (HBx) / RNA polymerase / Transactivation / TFIIB / RPB5-mediating protein, RMP / p53 / TFIB |
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| Research Abstract |
HBx has been suspected to have positive roles in hepatocarcinogenesis. Previously e reported that RNA polymerase II subunit 5 (RPB5) is one of the targets of HBx, suggesting a possibility that HBx may modulate transcription machinery. Our main results are following. 1).The trimeric interaction among HBx, RPB5 and TFIIB is necessary for HBx transactivation since the substitution mutants defective in binding either to TFIIB or RPB5 are impaired in transacting ability (J.Biol. Chem., 272 : 317 (1997)). 2)By in vivo and in vitro transcription assays, GaIDB-fused HBx can not act as transcriptional activator, but HBx augmented activated transcription by Gal-VP16, indicating that HBx can act as a coactivator (J.Biol. Chem., (1998)). 3)We isolated a novel RPB5-mediating protein (RMP) by a far Western cloning. RMP strongly bound RPB5 but neither HBx nor TBP in vitro and in vivo. RMP counteracts HBx transactivation in a dose dependent manner. Furthermore, RMP acts as a co-repressor since it inhibits transcriptional activation by Gal-VPl6. These RMP functions requires its RPB5-binding region, suggesting that these functional interference is due to competition between HBx and RMP to bind RMP.These results suggest that RMP negatively modulates transcription process at the interaction step between RPB5 and TFIIB which might be the target process of HBx (Mol. Cell. Biol., (1998)). 4)HBx interacts with p53 and interferes p53-dependent transactivation. However, the interference of the p53 function by HBx is distinct from the transactivation of HBx (Cancer Res., (1997)).
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