| Project/Area Number |
21590113
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | Kyoto Pharmaceutical University (2011)
University of Yamanashi (2009-2010) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
平 敬宏 山梨大学, 大学院・医学工学総合研究部, 教授 (70197036)
王賀 理恵 山梨大学, 医学部, 助手 (00160432)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ウイルス / リン酸化 / タンパク質分解 / 創薬 / プロセッシング / 抗ウイルス薬 / 感染症 / 酵素 / 基質特異性 / がん / リンパ腫 |
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| Research Abstract |
Kaposi's sarcoma associated herpesvirus(KSHV), also known as human herpesvirus 8, is associated with Kaposi's sarcoma(KS) and AIDS-related primary effusion lymphoma(PEL). Here we have elucidated functions and intracellular metabolisms of KSHV encoded proteins, such as ORF21, ORF36 and ORF73. ORF21 and ORF36 functions as nucleoside and protein kinase, respectively. Interestingly, ORF36 can phosphorylate Rb, resulting in activation of E2F and progression to S phase. It have been known that ORF73, latency-associated nuclear antigen(LANA) of KSHV is required for maintenance of KSHV DNA and is believed to play an important role in KSHV latency and tumorigenesis. We have studied the metabolisms and post-translational processing of LANA. We found that a relatively small number of full-length LANA proteins are cleaved at C-terminal region and produced C-terminal fragments of LANA, causing anti-apoptosis. Furthermore, we found several anti KSHV agents, which suppress the KSHV DNA replication.
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