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Interferon regulatory factor-4 activates IL-2 and IL-4 promoters in cooperation with c-Rel.
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作成者 |
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権利情報 |
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Copyright © 2011 Elsevier Ltd. All rights reserved.
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主題 |
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Other
Adult T-cell leukemia/lymphoma (ATLL)
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C-Rel
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IL-2
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IL-4
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Interferon regulatory factor (IRF)-4
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内容注記 |
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Interferon regulatory factor (IRF)-4 is a member of the IRF transcription factor family, whose expression is primarily restricted to lymphoid and myeloid cells. In T-cells, IRF-4 expression is induced by T-cell receptor (TCR) cross-linking or treatment with phorbol-12-myristate-13-acetate (PMA)/Ionomycin, and IRF-4 is thought to be a critical factor for various functions of T-cells. To elucidate the IRF-4 functions in human adult T-cell leukemia virus type 1 (HTLV-1)-infected T-cells, which constitutively express IRF-4, we isolated IRF-4-binding proteins from T-cells, using a tandem affinity purification (TAP)-mass spectrometry strategy. Fourteen proteins were identified in the IRF-4-binding complex, including endogenous IRF-4 and the nuclear factor-kappaB (NF-κB) family member, c-Rel. The specific association of IRF-4 with c-Rel was confirmed by immunoprecipitation experiments, and IRF-4 was shown to enhance the c-Rel-dependent binding and activation of the interleukin-4 (IL-4) promoter region. We also demonstrated that IL-2 production was also enhanced by exogenously-expressed IRF-4 and c-Rel in the presence of P/I, in T-cells, and that the optimal IL-2 and IL-4 productions in vivo was IRF-4-dependent using IRF-4-/- mice. These data provide molecular evidence to support the clinical observation that elevated expression of c-Rel and IRF-4 is associated with the prognosis in adult T-cell leukemia/lymphoma (ATLL) patients, and present possible targets for future gene therapy.
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identifier:Cytokine, 56(3), pp.564-572; 2011
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出版者 |
Elsevier Ltd.
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日付 |
Created2020-12-22
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Issued2011-12
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言語 |
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資源識別のタイプ |
journal article |
出版タイプ |
AM |
資源識別子 |
URI
http://hdl.handle.net/10069/27006
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関連 |
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PMID
21890374
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DOI
https://doi.org/10.1016/j.cyto.2011.08.014
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収録誌情報 |
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ISSN
1043-4666
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ISSN
1096-0023
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Cytokine
56(3), 564-572
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ファイル |
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コンテンツ更新日時 |
2021-02-17 |