Di Palma Tina, D'Andrea Barbara, Liguori Giovanna Lucia, Liguoro Annamaria, de Cristofaro Tiziana, Del Prete Dolores, Pappalardo Andrea, Mascia Anna, Zannini Mariastella
Istituto di Endocrinologia e Oncologia Sperimentale G. Salvatore-CNR and Dpt. Biologia e Patologia Cellulare e Molecolare, Universita' di Napoli Federico II, Via S. Pansini 5, 80131 Napoli, Italy.
Exp Cell Res. 2009 Jan 15;315(2):162-75. doi: 10.1016/j.yexcr.2008.10.016. Epub 2008 Oct 28.
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.
Pax8和TTF-1是参与甲状腺形态发生以及甲状腺特异性基因转录调控的转录因子。这两种蛋白质仅在少数组织中表达,但它们同时存在的情况仅发生在甲状腺中,在那里它们在物理和功能上相互作用,从而调节作为甲状腺分化表型标志物的基因。TAZ是一种转录共激活因子,可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。最近在肺中证实的TAZ与TTF-1之间的物理和功能相互作用,引发了TAZ在甲状腺中是否也可能是重要调节分子的问题。在本研究中,我们证明了TAZ在甲状腺细胞中的存在,以及TAZ与转录因子Pax8和TTF-1在调节甲状腺基因表达方面存在重要合作。此外,我们发现这三种蛋白质在分化的甲状腺细胞核中共表达,并且TAZ在体外和体内均与Pax8和TTF-1相互作用。更重要的是,我们表明这种相互作用导致Pax8和TTF-1对甲状腺球蛋白启动子的转录活性显著增强,从而提示TAZ在控制参与甲状腺发育和分化的基因中发挥作用。