@article{oai:nagasaki-u.repo.nii.ac.jp:00012816, author = {Shindo, Hisakazu and Yasui, Kiyoshi and Yamamoto, Kazuo and Honma, Kiri and Yui, Katsuyuki and Kohno, Tomoko and Ma, Yuhua and Chua, Koon Jiew and Kubo, Yoshinao and Aihara, Hitoshi and Ito, Takashi and Nagayasu, Takeshi and Matsuyama, Toshifumi and Hayashi, Hideki}, issue = {3}, journal = {Cytokine}, month = {Dec}, note = {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., Cytokine, 56(3), pp.564-572; 2011}, pages = {564--572}, title = {Interferon regulatory factor-4 activates IL-2 and IL-4 promoters in cooperation with c-Rel.}, volume = {56}, year = {2011} }