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Title
  • Interferon regulatory factor-4 activates IL-2 and IL-4 promoters in cooperation with c-Rel.
Creator

Shindo, Hisakazu

Yasui, Kiyoshi

Yamamoto, Kazuo

Honma, Kiri

Yui, Katsuyuki

Kohno, Tomoko

Ma, Yuhua

Chua, Koon Jiew

Kubo, Yoshinao

Aihara, Hitoshi

Ito, Takashi

Nagayasu, Takeshi

Matsuyama, Toshifumi

Hayashi, Hideki

Rights
    • Copyright © 2011 Elsevier Ltd. All rights reserved.
Subject
  • Other Adult T-cell leukemia/lymphoma (ATLL)
  • Other C-Rel
  • Other IL-2
  • Other IL-4
  • Other Interferon regulatory factor (IRF)-4
Description
Other
  • 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.
Other
  • identifier:Cytokine, 56(3), pp.564-572; 2011
Other
  • identifier:10960023
PublisherElsevier Ltd.
Date Issued 2011-12
Languageeng
NIItypejournal article
VersiontypeAM
Identifier URI http://hdl.handle.net/10069/27006
Relation
  • isIdenticalTo PMID 21890374
  • isIdenticalTo DOI https://doi.org/10.1016/j.cyto.2011.08.014
Journal
    • ISSN 1043-4666
    • Cytokine
    56(3), 564-572
File
Oaidate2014-06-23T05:18:13Z