https://scholars.lib.ntu.edu.tw/handle/123456789/416277
標題: | Ets-1 facilitates nuclear entry of NFAT proteins and their recruitment to the IL-2 promoter | 作者: | Tsao, Hsiao-Wei Tai, Tzong-Shyuan Tseng, William Chang, Hui-Hsin Grenningloh, Roland SHI-CHUEN MIAW Ho, I-Cheng |
公開日期: | 24-九月-2013 | 出版社: | NATL ACAD SCIENCES | 卷: | 110 | 期: | 39 | 起(迄)頁: | 15776 | 來源出版物: | Proceedings of the National Academy of Sciences of the United States of America | 摘要: | E26 transformation-specific sequence 1 (Ets-1), the prototype of the ETS family of transcription factors, is critical for the expression of IL-2 by murine Th cells; however, its mechanism of action is still unclear. Here we show that Ets-1 is also essential for optimal production of IL-2 by primary human Th cells. Although Ets-1 negatively regulates the expression of Blimp1, a known suppressor of IL-2 expression, ablation of B lymphocyte-induced maturation protein 1 (Blimp1) does not rescue the expression of IL-2 by Ets-1-deficient Th cells. Instead, Ets-1 physically and functionally interacts with the nuclear factor of activated T-cells (NFAT) and is required for the recruitment of NFAT to the IL-2 promoter. In addition, Ets-1 is located in both the nucleus and cytoplasm of resting Th cells. Nuclear Ets-1 quickly exits the nucleus in response to calcium-dependent signals and competes with NFAT proteins for binding to protein components of noncoding RNA repressor of NFAT complex (NRON), which serves as a cytoplasmic trap for phosphorylated NFAT proteins. This nuclear exit of Ets-1 precedes rapid nuclear entry of NFAT and Ets-1 deficiency results in impaired nuclear entry, but not dephosphorylation, of NFAT proteins. Thus, Ets-1 promotes the expression of IL-2 by modulating the activity of NFAT. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84884608815&doi=10.1073%2fpnas.1304343110&partnerID=40&md5=8c5c5bd008990f9521cc93470a0e759a https://scholars.lib.ntu.edu.tw/handle/123456789/416277 |
ISSN: | 0027-8424 | DOI: | 10.1073/pnas.1304343110 |
顯示於: | 免疫學研究所 |
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