FIAT control of osteoblast activity.
FIAT control of osteoblast activity.
复制标题
FIAT 控制成骨细胞活性。
DOI：
10.1002/jcb.22435
复制
发表时间：
2010
影响因子：
4
通讯作者：
Mandic,Vice
中科院分区：
文献类型：
--
作者：
St-Arnaud,René;Mandic,Vice
碱性结构域-亮氨酸拉链转录因子激活转录因子4（ATF 4）调节成骨细胞的大多数功能。因此，它的活动应通过几种机制加以管制，这并不奇怪。抑制ATF 4介导的转录的因子（FIAT）是一种亮氨酸拉链核分子，缺乏与ATF 4相互作用以抑制其转录活性的DNA结合的基本结构域。在成骨细胞生成过程中，与ATF 4平行监测FIAT表达。通过结构-功能分析探讨FIAT抑制ATF 4的机制。通过RNA干扰沉默成骨细胞中的FIAT，以及通过表征两种遗传小鼠模型：在成骨细胞中过表达FIAT的FIAT转基因小鼠和FIAT敲除小鼠，研究了FIAT在成骨细胞中表达的生理意义。迄今为止的研究表明，FIAT和ATF 4在成骨细胞中共表达，FIAT对基质矿化的抑制需要通过第二个亮氨酸拉链与ATF 4二聚化。此外，过表达FIAT的转基因小鼠表现出骨质减少。FIAT基因敲除小鼠的表型仍在评估中，但在这里讨论的突出方面。总之，迄今为止积累的结果支持FIAT是一种调节成骨细胞功能的转录抑制因子的假设。J.细胞。109：453-459，2010.© 2009 Wiley利斯公司
The basic domain‐leucine zipper transcription factor activating transcription factor 4 (ATF4) regulates most functions of the osteoblast. It is therefore not surprising that its activity should be regulated through several mechanisms. Factor inhibiting ATF4‐mediated transcription (FIAT) is a leucine zipper nuclear molecule lacking a basic domain for DNA binding that interacts with ATF4 to repress its transcriptional activity. FIAT expression was monitored in parallel with ATF4 during osteoblastogenesis. The mechanism of ATF4 repression by FIAT was investigated through structure–function analysis. The physiological significance of FIAT expression in osteoblasts was studied through silencing FIAT in osteoblasts by RNA interference, as well as through characterization of two genetic mouse models: FIAT transgenic mice which overexpress FIAT in osteoblasts, and FIAT knockout mice. Studies to date show that FIAT and ATF4 are co‐expressed in osteoblasts, and that FIAT inhibition of matrix mineralization requires dimerization with ATF4 through the second leucine zipper. Furthermore, transgenic mice overexpressing FIAT exhibit osteopenia. The phenotype of FIAT knockout mice is still under evaluation but the salient aspects are discussed here. Taken together, the results accumulated to date support the hypothesis that FIAT is a transcriptional repressor that modulates osteoblast function. J. Cell. Biochem. 109: 453–459, 2010. © 2009 Wiley‐Liss, Inc.