2011 Fiscal Year Final Research Report
functional analysis of human herpesvirus encoded kinases
| 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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| Project Period (FY) |
2009 – 2011
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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 |
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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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Author(s)
Niinaka Y, Harada K, Fujimuro M, Oda M, Haga A, Hosoki M, Uzawa N, Arai N, Yamaguchi S, Yamashiro M, and Raz A
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Journal Title
Cancer Res
Volume: 70
Pages: 9483-9493
Peer Reviewed
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Author(s)
Ikeda O, Miyasaka Y, Yoshida R, Mizushima A, Oritani K, Sekine Y, Kuroda M, Yasui T, Fujimuro M, Muromoto R, Nanbo A, Matsuda T
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Journal Title
FEBS Lett
Volume: 584
Pages: 865-872
Peer Reviewed
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