NFAT公司
转录因子
钙调神经磷酸酶
免疫沉淀
异位表达
基因亚型
化学
结合位点
生物
细胞生物学
分子生物学
基因
生物化学
移植
外科
医学
作者
Noriko Kitamura,Mayumi Shindo,Jun Ohtsuka,Akira Nakamura,Masaru Tanokura,Takachika Hiroi,Osamu Kaminuma
摘要
Abstract Nuclear factor of activated T cells (NFAT) leads to the transcription of diverse inducible genes involved in many biological processes; therefore, aberrant NFAT expression is responsible for the development and exacerbation of various disorders. Since five isoforms of NFAT (NFATc1‐c4, NFAT5) exhibit distinct and overlapping functions, selective control of a part, but not all, of NFAT family members is desirable. By comparing the binding activity of each NFATc1‐c4 with its regulatory enzyme, calcineurin (CN), using a quantitative immunoprecipitation assay, we found a new CN‐binding region (CNBR) selectively functioning in NFATc1 and NFATc4. This region, termed CNBR3, is located between two preexisting CNBR1 and CNBR2, within the Ca 2+ regulatory domain. The nuclear translocation of NFATc1 but not NFATc2 in T cells was suppressed by ectopic expression of CNBR3 and, accordingly, NFATc1‐dependent cytokine expression was downregulated. Through competition assays using NFATc1‐derived partial peptides and mass spectrometry with photoaffinity technology, we identified 18 amino acids in NFATc1 (Arg 258 to Pro 275 ) and 13 amino acids in CN catalytic subunit (CNA) (Asn 77 to Gly 89 ) responsible for CNA/CNBR3 binding in which Cys 263 and Asp 82 , respectively, played crucial roles. The possible selective regulation of NFAT‐mediated biological processes by targeting this new CN/NFAT‐binding region is suggested.
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