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FIAT, the factor-inhibiting ATF4-mediated transcription, also represses the transcriptional activity of the bZIP factor FRA-1

机译:菲亚特,抑制ATF4介导的转录,还抑制了BZIP因子FRA-1的转录活性

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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-9 and Mgp. 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.
机译:菲亚特是一种亮氨酸拉链蛋白,其名称是与ATF4的相互作用,并随后对ATF4定向的骨钙基因转录进行堵塞。菲亚特缺乏基本的DNA装订域,但包含三个亮氨酸拉链;它与ATF4杂交,以禁止与DNA结合。菲亚特还可以与额外的基本域 - 亮氨酸拉链转录调节剂相互作用,例如FRA-1。我们发现菲亚特抑制了FRA-1 / C-Jun异二聚体的转录激活,而不影响由C-Jun同源过二聚体介导的转录。使用Natural FRA-1靶,MMP-9和MGP的报道构建体测量菲亚特对FRA-1依赖性转录的阻遏物效应。 FIAT-FRA-1相互作用通过菲亚特的第二亮氨酸拉链介导。这些数据证实了菲亚特转录阻遏物活性的额外目标,并表明菲亚特可以通过与ATF4相互作用来调节早期成骨细胞活性,并通过抑制FRA-1来调节后续成骨细胞函数。

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