TAZ is a coactivator for Pax8 and TTF-1, two transcription factors involved in thyroid differentiation
TAZ is a coactivator for Pax8 and TTF-1, two transcription factors involved in thyroid differentiation
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DOI：
10.1016/j.yexcr.2008.10.016
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发表时间：
2009-01-15
影响因子：
3.7
通讯作者：
Zannini, Mariastella
中科院分区：
文献类型：
--
作者：
Di Palma, Tina;D'Andrea, Barbara;Zannini, Mariastella
Pax 8和TTF-1是参与甲状腺形态发生和甲状腺特异性基因转录调控的转录因子。这两种蛋白质在少数组织中表达，但它们同时存在仅发生在甲状腺中，在甲状腺中它们在物理上和功能上相互作用，允许调节作为甲状腺分化表型标志物的基因。TAZ是一种转录辅激活因子，调节多种转录因子的活性，因此在组织特异性转录中发挥核心作用。最近证实TAZ和TTF-1在肺中的物理和功能相互作用提出了TAZ是否也可以在甲状腺中成为重要的调节分子的问题。在这项研究中，我们证明了TAZ在甲状腺细胞中的存在，以及TAZ与转录因子Pax 8和TTF-1在甲状腺基因表达调控中的重要合作。此外，我们揭示了这三种蛋白质在分化的甲状腺细胞的细胞核中共表达，并且TAZ在体外和体内与Pax 8和TTF-1相互作用。更重要的是，我们发现这种相互作用导致Pax 8和TTF-1在甲状腺球蛋白启动子上的转录活性显著增强，从而表明TAZ在控制甲状腺发育和分化相关基因中的作用。(C)2008年爱思唯尔公司All rights reserved.
Pax8 and TTF-1 are transcription factors involved in the morphogenesis of the thyroid gland and in the transcriptional regulation of thyroid-specific genes. Both proteins are expressed in few tissues but their simultaneous presence occurs only in the thyroid where they interact physically and functionally allowing the regulation of genes that are markers of the thyroid differentiated phenotype. TAZ is a transcriptional coactivator that regulates the activity of several transcription factors therefore playing a central role in tissue-specific transcription. The recently demonstrated physical and functional interaction between TAZ and TTF-1 in the lung raised the question of whether TAZ could be an important regulatory molecule also in the thyroid. In this study, we demonstrate the presence of TAZ in thyroid cells and the existence of an important cooperation between TAZ and the transcription factors Pax8 and TTF-1 in the modulation of thyroid gene expression. In addition, we reveal that the three proteins are co-expressed in the nucleus of differentiated thyroid cells and that TAZ interacts with both Pax8 and TTF-1, in vitro and in vivo. More importantly, we show that this interaction leads to a significant enhancement of the transcriptional activity of Pax8 and TTF-1 on the thyroglobulin promoter thus suggesting a role of TAZ in the Control of genes involved in thyroid development and differentiation. (C) 2008 Elsevier Inc. All rights reserved.