Dual Role of Sumoylation in the Nuclear Localization and Transcriptional Activation of NFAT1*
Dual Role of Sumoylation in the Nuclear Localization and Transcriptional Activation of NFAT1*
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DOI：
10.1074/jbc.m403153200
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发表时间：
2004-07
影响因子：
4.8
通讯作者：
Y. Terui;Natalie Saad;S. Jia;F. McKeon;Junying Yuan
中科院分区：
文献类型：
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作者：
Y. Terui;Natalie Saad;S. Jia;F. McKeon;Junying Yuan
活化T细胞核因子（NFAT）转录因子的核输入对于调节NFAT活性至关重要。在这里，我们表明，SUMO化NFAT 1定义了一种新的机制，从已知的钙调神经磷酸酶介导的去磷酸化和核进口的核锚定和转录激活下游。我们发现NFAT 1的Lys 684和Lys 897可以被sumoylated。在Lys 684处的类小泛素化是NFAT 1转录活性和随后的Lys 897类小泛素化所需的，而Lys 897类小泛素化仅是核锚定所需的。由于NFAT 1的Lys 897在NFAT家族的其他成员中不保守，我们建议Lys 897的SUMO化可能为NFAT 1的核锚定和转录激活的同种型特异性调节提供机制。此外，我们发现，治疗与离子霉素和佛波醇12-肉豆蔻酸酯13-乙酸酯确保有效的核锚定与招聘NFAT 1到SUMO-1机构，而治疗与离子霉素单独诱导核转位NFAT 1，但不招聘到SUMO-1机构。我们的研究结果表明，招聘NFAT 1到SUMO-1机构可能需要的NFAT 1的渐进式转录活性后，共刺激与离子霉素和佛波醇12-肉豆蔻酸酯13-乙酸酯，而无反应性转录刺激离子霉素单独可能会发生没有招聘到SUMO-1机构。
The nuclear import of nuclear factor of activated T cells (NFAT) transcription factors is critical for regulating NFAT activity. Here we demonstrate that the sumoylation of NFAT1 defines a novel mechanism of the nuclear anchorage and transcriptional activation downstream from the known mechanism of calcineurin-mediated dephosphorylation and nuclear import. We show that Lys684 and Lys897 of NFAT1 can be sumoylated. The sumoylation at Lys684 is required for NFAT1 transcriptional activity and subsequent sumoylation of Lys897, whereas the sumoylation of Lys897 is only required for nuclear anchorage. Because Lys897 of NFAT1 is not conserved among other members of the NFAT family, we propose that sumoylation of Lys897 may provide a mechanism for NFAT1 isotype-specific regulation of nuclear anchorage and transcriptional activation. Furthermore, we found that treatment with both ionomycin and phorbol 12-myristate 13-acetate ensured efficient nuclear anchorage with the recruitment of NFAT1 into the SUMO-1 bodies, whereas treatment with ionomycin alone induced nuclear translocation of NFAT1 but not recruitment into the SUMO-1 bodies. Our results suggest that the recruitment of NFAT1 into SUMO-1 bodies may be required for the progressive transcriptional activity of NFAT1 upon co-stimulation with ionomycin and phorbol 12-myristate 13-acetate, whereas anergic transcription stimulated by ionomycin alone may occur without recruitment into the SUMO-1 bodies.