Molecular mechanism of arsenite therapy against adult T-cell leukemia
| Project/Area Number |
23591376
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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 |
Hematology
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| Research Institution | Niigata University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ATL / 白血病 / 亜砒酸 / USP10 / ストレス顆粒 / G3BP1 / ROS / HTLV-1 / ＡＴＬ / stress granules / 亜ヒ酸 / アポトーシス |
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| Research Abstract |
HTLV-1 is a causative agent of adult T-cell leukemia (ATL). Combination therapy containing arsenite has been shown to be effective to ATL patients.
In this study, we identified that USP10 as a binding partner of HTLV-1 Tax oncoprotein. We established USP10 knockout mice and its knockout cells. USP10 mutants in USP10-knockout cells indicated that USP10 inhibits arsenite-induced apoptosis by reducing ROS production by forming stress granules. USP10 interacted with G3BP1 and the interaction is critical for inhibition of apoptosis induced by arsenite. USP10 knockdown in T-cells augmented apoptosis induced by arsenite. Arsenite induced more apoptosis in ATL cells than HTLV-1-uninfected T-cell lines. Tax augmented arsenite-induced apoptosis in cells, and the augmentation needs the interaction with USP10. These results indicated that USP10 is a cellular protein controlling sensitivity of leukemia T-cells to arsenite therapy.
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Report
(4 results)
Research Products
(55 results)
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[Journal Article] Failure in activation of the NF-kB canonical pathway by human T-cell leukemia virus type 1 Tax in non-hematopoietic cell lines2013
Author(s)
Mizukoshi T, Komori H, Mizuguchi M, Abdelaziz H, Hara T, Higuchi M, Tanaka Y, Ohara Y, Funato N, Fujii M, Nakamura M
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Journal Title
Virology
Volume: 443(2)
Pages: 226-235
Related Report
Peer Reviewed
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