| Project/Area Number |
25830126
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor therapeutics
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| Research Institution | The University of Tokyo (2014)
Institute of Physical and Chemical Research (2013) |
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Principal Investigator |
ISHIHARA Makoto 東京大学, 新領域創成科学研究科, 客員共同研究員 (60581189)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | プロテオミクス / HTLV-1 / 膜プロテオーム / 糖鎖 |
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| Outline of Final Research Achievements |
Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus which infects CD4+ T-cells and induce Adult T-cell leukemia (ATL). To develop novel targeted therapies for ATL, we conducted mass spectrometry-based membrane proteome analysis on CD4+ T-cells, isolated from normal donors (n = 14), asymptomatic carriers (n = 21), ATL (n = 13), and HTLV-1 associated myelopathy patients (n = 21). To focus on membrane proteome, glycopeptides were enriched from tryptic digests of CD4+ T-cells with ConA-affinity chromatography. LC-MS/MS analysis of 69 samples allowed identification of 946 N-glycoproteins (FDR < 0.01). As a consequence of Welch’s t-test, growth-regulatory adhesion molecule (GRAM) was identified as one of upregulated proteins in ATL. Real-time PCR revealed CD4+GRAM+ subpopulation was enriched with infected cells, indicating GRAM is a promising target for ATL. These results showed our comprehensive membrane-proteome analysis is suited for screening of novel therapeutic targets.
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