Quantitative membrane-proteome analysis to discover novel therapeutic targets for adult T-cell leukemia (ATL)

2014 Fiscal Year Final Research Report

• Project/Area Number: 25830126
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: The University of Tokyo (2014); Institute of Physical and Chemical Research (2013)
• 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)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: プロテオミクス / HTLV-1

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.

Free Research Field

プロテオミクス