2000 Fiscal Year Final Research Report Summary
Constitutive activation of LIL-Stat in adult T cell leukemia cells
| Project/Area Number |
10670976
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
TSUKADA Junichi Univ.of Occupational Environmental Health, School of Medicine, Associate Professor, 医学部, 助教授 (20227367)
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| Co-Investigator(Kenkyū-buntansha) |
ETO Sumiya Univ.of Occupational Environmental Health, School of Medicine, Professor, 医学部, 教授 (90010347)
MISAGO Masahiro Univ.of Occupational Environmental Health, School of Health Sciences, Associate Professor, 産業保健学部, 助教授 (30157474)
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| Project Period (FY) |
1998 – 2000
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| Keywords | adult T cell leukemia / interleukin 1 / gene transcription / cvtokine / STAT / Receptor / leukemia / signal transduction |
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| Research Abstract |
Binding of many cytokines to their cognate receptors immediately activates Jak tyrosine kinases and their substrates ; namely, STAT (signal transducers and activators of transcription) DNA binding proteins. The activated STAT proteins dimerize and are translocated to the nucleus in order to transactivate genes by binding to variations on the gamma interferon (IFN-γ) activation site (GAS).
We have recently demonstrated that both lipopolysaccharide (LPS) and IL-1 immediately activate a common novel STAT factor. This LPS/IL-1 inducible factor (LIL-Stat) binds a GAS-like sequence (TTCCTGAGA) termed LILRE (LPS and IL-1 responsive element) in the human prointerleukin 1β (IL1B) gene and is recognized by an antibody (Ab) raised to the N-terminus of Stat1 (anti-Stat1N Ab), but not by those specific for either the C terminus of Stat1 (anti-Stat1C Ab) or any other GAS-binding STAT.The DNA-binding activity of this protein is inhibited by phosphotyrosine, suggesting that phosphotyrosine mediates the
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obligate dimerization required for STAT DNA binding. Analysis of DNA binding specificity has demonstrated that the LIL-Stat possesses a novel GAS-like binding activity that contrasts with that of other STATs in a requirement for a G residue at position 8. The existence of such a factor relates the signaling pathway for IL-1 and LPS receptors to other cytokine receptors that mediate signaling via the immediate activation of STAT transcriptional factors.
In the present study, we investigated LIL-Stat activation status in ATL cells by electrophoretic mobility shift assay (EMSA) using a radiolabeled LILRE probe and ATL cell nuclear extracts. The functional role of LIL-Stat in ATL cells was further assessed by transient transfection studies using LILRE chloramphenicol acetyltransferase (CAT) reporters. As a result, spontaneous DNA binding of LIL-Stat was observed in all ATL cells examined. However, in normal human peripheral lymphocytes, DNA binding of LIL-Stat was detected only after stimulation with IL-1. These results demonstrated that LIL-Stat is constitutively activated in ATL cells. Furthermore, our transient transfection studies using LILRE chloramphenicol acetyltransferase (CAT) reporters argue that LIL-Stat in ATL cells functions as a transcriptional activator through binding to the LILRE in the IL1B gene. Less
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Research Products
(16 results)
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[Publications] Tanaka Y, Minami Y, Mine S, Hirano H, Hu CD, Fujimoto H, Fujii K, Saito K, Tsukada J, van Kooyk Y, Figdor CG, Kataoka T, Eto S: "H-Ras signals to cytoskeletal machinery in induction of integrin-mediated adhesion of T cells."J Immunol.. 163(11). 6209-16 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Marmiroli S, Bavelloni A, Faenza I, Sirri A, Ognibene A, Cenni V, Tsukada J, Koyama Y, Ruzzene M, Ferri A, Auron PE, Toker A, Maraldi NM: "Phosphatidylinositol 3-kinase is recruited to a specific site in the activated IL-1 receptor I."FEBS Lett.. 438(1-2). 49-54 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Tanaka Y, Mine S, Figdor CG, Wake A, Hirano H, Tsukada J, Aso M, Fujii K, Saito K, van Kooyk Y, Eto S: "Constitutive chemokine production results in activation of leukocyte function-accociated antigen-1 on adult T-cell leukemia cells."Blood.. 91(10). 3909-19 (1998)
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「研究成果報告書概要(欧文)」より
