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

• DOI: 10.1073/pnas.1304343110
• Publication Date: 2013-09-10T02:31:16Z
• Authors: Hsiao-Wei Tsao; Tzong-Shyuan Tai; William Tseng; Hui-Hsin Chang; Roland Grenningloh; Shi-Chuen Miaw; I-Cheng Ho
• Keywords: Cell Nucleus; 0301 basic medicine; Base Sequence; NFATC Transcription Factors; Molecular Sequence Data; Th1 Cells; Proto-Oncogene Protein c-ets-1; Gene Knockout Techniques; Mice; Protein Transport; 03 medical and health sciences; Multiprotein Complexes; Animals; Humans; Interleukin-2; Calcium; Positive Regulatory Domain I-Binding Factor 1; Promoter Regions, Genetic; Protein Binding; Signal Transduction; Transcription Factors

Significance IL-2 plays critical roles in many immune responses. However, its transcriptional regulation is still not fully understood. Data described in this paper demonstrate that the transcriptional factor E26 transformation-specific sequence 1 (Ets-1) promotes the expression of IL-2 by nuclear factor of activated T-cells (NFAT)-dependent mechanisms. Nuclear Ets-1 synergizes with NFAT in the transcription of IL-2. Ets-1 is also translocated to the cytoplasm in response to calcium-induced signals and facilitates the release of NFAT from noncoding RNA repressor of NFAT complex, which traps NFAT in the cytoplasm. This paper not only advances our understanding of the transcriptional regulation of IL-2 but also depicts a unique mechanism of action of Ets-1.