FIAT, the factor-inhibiting ATF4-mediated transcription, also represses the transcriptional activity of the bZIP factor FRA-1.
FIAT, the factor-inhibiting ATF4-mediated transcription, also represses the transcriptional activity of the bZIP factor FRA-1.
复制标题
FIAT 是 ATF4 介导的转录抑制因子，也抑制 bZIP 因子 FRA-1 的转录活性。
DOI：
10.1111/j.1749-6632.2009.05211.x
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发表时间：
2010
影响因子：
5.2
通讯作者：
Elchaarani,Bilal
中科院分区：
文献类型：
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作者：
St-Arnaud,Rene;Mandic,Vice;Elchaarani,Bilal
FIAT是一种亮氨酸拉链蛋白，其命名是因为它与ATF4相互作用，并随后阻止ATF4导向的骨钙素基因转录。菲亚特缺乏一个基本的DNA结合域，但包含三个亮氨酸拉链；它与ATF4异源二聚，以阻止与DNA的结合。FIAT还可能与成骨细胞活性的其他碱性结构域-亮氨酸拉链转录调节因子，如FRA-1相互作用。我们发现，FIAT抑制FRA-1/c-Jun异源二聚体的转录激活，而不影响c-Jun同源二聚体介导的转录。利用天然FRA-1靶标基质金属蛋白酶-9和镁蛋白的报告构建体，检测菲亚特对FRA-1依赖转录的抑制作用。菲亚特与FRA-1的相互作用是通过菲亚特的第二个亮氨酸拉链调节的。这些数据证实了FIAT转录抑制活性的另一个靶点，并表明FIAT既可以通过与ATF4相互作用来调节早期成骨细胞的活性，也可以通过抑制FRA-1来调节晚期成骨细胞的功能。
FIAT is a leucine zipper protein whose name was coined for its interaction with ATF4 and subsequent blockage of ATF4‐directed osteocalcin gene transcription. FIAT lacks a basic DNA‐binding domain but contains three leucine zippers; it heterodimerizes with ATF4 to prohibit binding to DNA. FIAT could also potentially interact with additional basic domain‐leucine zipper transcriptional regulators of osteoblast activity, such as FRA‐1. We have found that FIAT inhibits transcriptional activation by a FRA‐1/c‐JUN heterodimer without affecting transcription mediated by a c‐JUN homodimer. The repressor effect of FIAT on FRA‐1‐dependent transcription was measured using reporter constructs for the natural FRA‐1 targets,Mmp‐9andMgp. The FIAT–FRA‐1 interaction is mediated through the second leucine zipper of FIAT. These data confirm an additional target of the FIAT transcriptional repressor activity and suggest that FIAT can both modulate early osteoblast activity by interacting with ATF4 and regulate later osteoblast function through inhibition of FRA‐1.