Implication of NMD inhibition by Rex to the host cell leukemogenesis
| Project/Area Number |
24501304
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Carcinogenesis
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NAKANO Kazumi 東京大学, 新領域創成科学研究科, 助教 (60549591)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Toshiki 東京大学, 大学院新領域創成科学研究科, 教授 (30182934)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | ＨＴＬＶ－１ / Ｒｅｘ / ＮＭＤ / ＡＴＬ / ウイルス発がん / HTLV-1 / Rex / NMD / ATL |
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| Outline of Final Research Achievements |
Nonsense-mediated mRNA decay (NMD) is a conserved cellular mRNA quality control mechanism. RNA signals to express viral genes potentially initiate NMD, nevertheless it is not clear how viruses evade NMD. Human-T-cell Leukemia Virus type-I (HTLV-1) is a retrovirus responsible for Adult T-cell Leukemia (ATL). Previously, we demonstrated that HTLV-1 Rex approves the stability of viral RNA by inhibiting NMD. In the present study, we focused on the molecular mechanism of NMD inhibition by Rex, and further clarified that the N-terminal region of Rex with unknown function (domain-X), was critical for effective suppression of NMD activity. We also showed that overexpression of Rex resulted in significant changes of more than 9,000 gene expression profiles in CEM human T cell line. Our results propose a possibility that Rex stabilizes the viral RNA by inhibition of NMD through the domain-X, and perturbs cellular mRNA metabolism and host cell homeostasis for its new function.
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Advanced HTLV-1 carriers and early-stage indolent ATLs are indistinguishable based on CADM1 positivity in flow cytometry2015
Author(s)
Kobayashi S, Watanabe E, Ishigaki T, Ohno N, Yuji K, Nakano K, Yamochi T, Watanabe N, Tojo A, Watanabe T, Uchimaru K.
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Journal Title
Cancer Sci
Volume: 印刷中
Issue: 5
Pages: 598-603
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] CADM1 expression and stepwise downregulation of CD7 are closely associated with clonal expansion of HTLV-I-infected cells in adult T-cell leukemia/lymphoma2014
Author(s)
Kobayashi S, Nakano K, Watanabe E, Ishigaki T, Ohno N, Yuji K, Oyaizu N, Asanuma S, Yamagishi M, Yamochi T, Watanabe N, Tojo A, Watanabe T, Uchimaru K
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Journal Title
Clinical Cancer Research
Volume: 20(11)
Issue: 11
Pages: 2851-61
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Viral interference with host mRNA surveillance, the nonsense-mediated mRNA decay (NMD) pathway, through a new function of HTLV-1 Rex: implications for retroviral replication.2013
Author(s)
Nakano, K., Ando, T., Yamagishi, M., Yokoyama, K., Ishida, T., Ohsugi, T., Tanaka, Y., Brighty, D. W. and Watanabe, T.
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Journal Title
Microbes and Infection
Volume: 15
Issue: 6-7
Pages: 491-505
DOI
Related Report
Peer Reviewed
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[Presentation] Human T-Lymphotropic Virus Type 1 Biomarkers in Patients with Rheumatoid Arthritis2014
Author(s)
Okayama A, Iwanaga M, Sagara Y, Hidaka T, Umekita K, Nakano K, Watanabe T, Yamano Y, Horai Y, Nakamura H, Kawakami A
Organizer
ACR/ARHP Annual Meeting
Place of Presentation
Boston, U.S.A
Year and Date
2014-11-18
Related Report
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[Presentation] Tumor-specific gene expression leads to p38 and Hedgehog signaling activation in adult T cell leukemia2014
Author(s)
Yamagishi M, Takahashi R, Sakai N, Fujikawa D, Nakagawa S, Yamochi T, Yamochi T, Nakano K, Uchimaru K, Utsunomiya A, Watanabe T
Organizer
第76回日本血液学会学術集会
Place of Presentation
大阪国際会議場、大阪
Year and Date
2014-10-31 – 2014-11-02
Related Report
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