2001 Fiscal Year Final Research Report Summary
Functional analysis of viral protein kinases and regulatory proteins for latency of herpes simples virus
| Project/Area Number |
12670276
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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 |
Virology
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| Research Institution | Tokyo Medical and Denta University |
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Principal Investigator |
KAWAGUCHI Yasushi Tokyo Medical and Dental University, Medical Research Institute, Associate Professor, 難治疾患研究所, 助教授 (60292984)
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| Project Period (FY) |
2000 – 2001
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| Keywords | HSV / ICP0 / UL13 / phosphorylation / BMAL1 |
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| Research Abstract |
Herpes simplex virus (HSV) is an important pathogen in human. In this research we focused on two viral regulatory proteins ICP0 and UL13. Furthermore, we tried to unveil novel features of these HSV regulatory proteins by analyzing functional homologs of lCP0 and UL13. The results obtained were as follows.
By yeast two-hybrid screening, we identified BMAL1, a member of basic helix-loop-helix (bHLH) PAS super family, as a new ICP0 binding partner. We found that ICP0 interacts with BMAL1 and stimulates BMAL1 dependent transcription. Furthermore, we demonstrated that ICP0 is involved in stabilization of BMAL1 in the cytoplasms of infected cells. Members of bHLH-PAS super-family are stress-related proteins and often play roles in adaptation to environmental changes. HSV is reactivated under stress conditions and it has been reported that ICP0 regulates reactivation from latency. Taken together, our findings suggest that the interaction between ICP0 and BMAL1 may play a role in viral reactiva
… More
tion from latency.
Epstein-Barr virus (EBV) also belongs to family Herpesviridae. We focused on EBV encoded protein kinase BGLF4 which is a homolog of HSV UL13. We succeeded to establish system for expression and purification of GST- and His-tagged BGLF4 using recombinant baculovirus. We also found that a cellular target of BGLF4 is translation factor EF- 1δ. We previously showed that HSV UL13 also phosphorylate EF-1δ. Taken together these results indicate that phosphorylation of EF- 1δ in infected cells is conserved function of all herpesviruses and EF- 1δ plays important role in various herpesvirus infections. We also focused on another EBV regulatory protein EBNA-LP which is suggested to be a functional homolog of HSV ICP0. Our results indicated that nuclear matrix association, nuclear localization, and phosphorylation by cellualr kinase(s) is essential to express co-activator function of EBNA-LP. ICP0 is also suggested to be phosphorylated by cellular kinase(s) and to be localized in nuclear matrix. These results suggest that cellular localization and phosphorylaton of ICP0 by cellular kinase(s) is also critical to express ICP0 functions. Less
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Research Products
(14 results)
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[Publications] <Y. Kawaguchi>____________-i, K. Nakajima, M. Igarashi, T. Morita, M. Tanaka, M. Suzuki, A. Yokoyama, G. Matsuda, K. Kato, M. Kanamori, and K. Hirai.: "Interaction of Epstein-Barr Virus nulear antigen leader protein (EBNA-LP) with HS1-associated protein X-1 : Implication of cytoplasmic function of EBNA-LP"J. Virol. 74. 10104-10111 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] K. Kato, <Y. Kawaguchi>____________-, M. Tanaka, Mie Igarashi, Akihiko Yokoyama, Go Matsuda, Mikiko Kanamori, Kaori Nakajima, Yorihiro Nishimura, Masayuki Shimojima, Hang T. T. Phung, Eiji Takahashi, and Kanji Hirai: "Epstein-Barr virus encoded-protein kinase BGLF mediates hyper-phosphorylation of celular elongation factor1δ(EF-1δ) : EF- 1δis universally modified by conserved protein tanases of herpesviruses"J. Gen. Virol.. 82. 1457-1463 (2001)
Description
「研究成果報告書概要(欧文)」より
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