TAZ is a coactivator for Pax8 and TTF-1, two transcription factors involved in thyroid differentiation.
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.
Di Palma
Tina
T
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.
D'Andrea
Barbara
B
Liguori
Giovanna Lucia
GL
Liguoro
Annamaria
A
de Cristofaro
Tiziana
T
Del Prete
Dolores
D
Pappalardo
Andrea
A
Mascia
Anna
A
Zannini
Mariastella
M
D000217:Acyltransferases; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006367:HeLa Cells; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013954:Thyroglobulin / Q000235:genetics / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D004268:DNA-Binding Proteins; C000614412:NKX2-1 protein, human; C000614414:Nkx2-1 protein, mouse; C000614416:Nkx2-1 protein, rat; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C499496:Pax8 protein, mouse; C499497:Pax8 protein, rat; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; C504004:Ttf1 protein, mouse; D013954:Thyroglobulin; D000217:Acyltransferases; C486363:tafazzin protein, mouse