Molecular regulatory mechanism of gene expression in immune system.
| Project/Area Number |
61480158
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | Osaka University |
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Principal Investigator |
TANIGUCHI TADATSUGU Institute for Molecular and Cellular Biology, Osaka University, 細胞工学センター, 教授 (50133616)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA GEN Institute for Molecular and Cellular Biology, Osaka University, 細胞工学センター, 助手 (80174712)
FUJITA TAKASHI Institute for Molecular and Cellular Biology, Osaka University, 細胞工学センター, 助手 (10156870)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1987: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1986: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | Interleukin-2 / Lymphokine / Il-2 Receptor / ATL / 成人性T細胞白血病 / 成人T細胞白血病 / リンフォカイン / 遺伝子発現 |
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| Research Abstract |
Interleukin-2 (IL-2) is a lymphokine which plays a key role in T cell growth and differentiation. We performed a series of studies in order to analyze molecular regulatory mechanism of IL-2 gene expression and T cell growth control which is mediated by the IL-2 system.
We cloned and analyzed the 5' flanking sequences of human IL-2 and IL-2 receptor (p55,Tac) gene and we identified functional DNA sequences controlling the IL-2 and IL-2R gene expression at the transcriptional level in activated T cells.
IL-2 system has also been studied in relation to the development of adult T cell leukemia/lymphoma (ATL). Our studies revealed that distinct DNA sequences of the 5' flanking region of IL-2 and IL-2R genes are responsible for the transcriptional activation by tat I (p40^x) protein which is encoded by HTLV-1. Furthermore, we showed that IL-2 gene is synergistically activated by tat I (p40^x) and extracellular stimulation mediated by T3/Ti complex. So the next emerging problem is to examine whether operation of IL-2 autocrine growth stimulation actually contributes to the generation of tumorigenic T cells or not. We constructed a recombinant retroviral Vector for IL-2 production in various cells, and by utilizing the virus we obtained results suggesting further the importance of aberrant operation of the IL-2 autocrine loop in the development of T cell marignancy.
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Report
(2 results)
Research Products
(17 results)
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[Publications] K,Hasegawa, M,Maruyama, T,Fujita, T,Ohashi, M,Hatakeyama, S,Minamoto, G,Yamada & T,Taniguchi: "Structure and regulation of the genes encoding interleukin-2 and its receptor." Regulation of Immune Gene Expression (M,Feldmann & A,McMichael eds.) The Humana Press Inc.85-93 (1986)
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[Publications] M,Maruyama, H,Shibuya, H,Harada, M,Hatakeyama, M,Seiki, T,Fujita, J-I,Inoue, M,Yoshida & T,Taniguchi: "Evidence for aberrant activation of the interleukin-2 autocrine loop by HTLV-1-encoded p40^x and T3/Ti complex triggering." Cell. 48. 343-350 (1987)
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[Publications] G,yamada, Y,Kitamura, H,Sonoda, H,Harada, S,Taki, R.C.Mulligan, H,Osawa, T,Diamantstein, S,Yokoyama & T,Taniguchi: "Retroviral expression of the human IL-2 gene in a murine T cell line results in cell growth autonomy and tumorigenicity." The EMBO Journal. 6. 2705-2709 (1987)
Description
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Related Report
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