NFATc2 recruits cJun homodimers to an NFAT site to synergistically activate interleukin-2 transcription

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• 作者：Ryan D. Walters ; Linda F. Drullinger ; Jennifer F. Kugel ; ^{jennifer.kugel@colorado.edu} ; James A. Goodrich ; ^{james.goodrich@colorado.edu}
• 关键词：Transcription ; NFAT ; cJun ; T cell ; Interleukin-2
• 刊名：Molecular Immunology
• 出版年：2013
• 出版时间：November, 2013
• 年：2013
• 卷：56
• 期：1-2
• 页码：48-56
• 全文大小：1109 K

文摘

Transcription of interleukin-2 (IL-2), a pivotal cytokine in the mammalian immune response, is induced by NFAT and AP-1 transcriptional activators in stimulated T cells. NFATc2 and cJun drive high levels of synergistic human IL-2 transcription, which requires a unique interaction between the C-terminal activation domain of NFATc2 and cJun homodimers. Here we studied the mechanism by which this interaction contributes to synergistic activation of IL-2 transcription. We found that NFATc2 can recruit cJun homodimers to the ?45 NFAT element, which lacks a neighboring AP-1 site. The bZip domain of cJun is sufficient to interact with the C-terminal activation domain of NFATc2 in the absence of DNA and this interaction is inhibited by AP-1 DNA. When the ?45 NFAT site was replaced by either an NFAT/AP-1 composite site or a single AP-1 site the specificity for cJun homodimers in synergistically activating IL-2 transcription was lost, and cJun/cFos heterodimers strongly activated transcription. These studies support a model in which IL-2 transcriptional synergy is mediated by the unique recruitment of a cJun homodimer to the ?45 NFAT site by NFATc2, where it acts as a co-activator for IL-2 transcription.