Ets-1 facilitates nuclear entry of NFAT proteins and their recruitment to the IL-2 promoter

Tsao H.-W.; Tai T.-S.; Tseng W.Chang H.-H.Grenningloh R.Miaw S.-C.Ho I.-C.

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Ets-1 facilitates nuclear entry of NFAT proteins and their recruitment to the IL-2 promoter

机译：Ets-1 facilitates nuclear entry of NFAT proteins and their recruitment to the IL-2 promoter

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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.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第39期|15776-15781|共6页
作者
Tsao H.-W.; Tai T.-S.; Tseng W.Chang H.-H.Grenningloh R.Miaw S.-C.Ho I.-C.;
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作者单位

Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, United States;

Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei 10051, Taiwan;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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正文语种英语
中图分类自然科学总论;
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nuclear; proteins; recreitment;

Ets-1 facilitates nuclear entry of NFAT proteins and their recruitment to the IL-2 promoter

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