Functional inactivation of the transcription factor Pax8 through oligomerization chain reaction

Molecular Endocrinology
Barbara D'AndreaMariastella Zannini

Abstract

Among the approaches used to provide a functional inactivation of a target protein, we have chosen the recently described oligomerization chain reaction (OCR) strategy to functionally inactivate the transcription factor Pax8, a member of the Pax gene family expressed in thyroid cells. The OCR strategy is based on the fusion of the self-associating coiled-coil (CC) domain of the nuclear factor promyelocytic leukemia (PML) to target proteins that are able to self-associate naturally or that form heterocomplexes. In the thyroid tissue, the transcription factor Pax8 is involved in the morphogenesis of the gland and in the transcriptional regulation of thyroid-expressed genes. We have recently demonstrated that in thyroid cells Pax8 interacts biochemically and functionally with the transcription factor TTF-1 (thyroid transcription factor 1), and that such interaction leads to the synergistic activation of thyroglobulin (Tg) gene expression. Fusion of the CC domain to Pax8 leads to the formation of aberrant, nonfunctional high-molecular mass complexes to which TTF-1 is also recruited. The CC-Pax8 chimera inhibits the transcriptional activity of Pax8 and of TTF-1 on both synthetic and physiological promoters and prevents the synergist...Continue Reading

Citations

Oct 20, 2012·Thyroid : Official Journal of the American Thyroid Association·Alessandra di GennaroRoberto Di Lauro
Apr 23, 2011·Molecular Biology and Evolution·Shinichiro HayashiFrederic Relaix
Oct 29, 2013·Antioxidants & Redox Signaling·Xavier De DekenFrançoise Miot
Mar 1, 2012·Molecular and Cellular Endocrinology·Christiane Christophe-HobertusDaniel Christophe
Dec 23, 2009·Molecular and Cellular Endocrinology·Henrik Fagman, Mikael Nilsson
Nov 18, 2008·Experimental Cell Research·Tina Di PalmaMariastella Zannini
Dec 22, 2006·Molecular and Cellular Endocrinology·Christiane Christophe-Hobertus, Daniel Christophe
May 18, 2007·Annual Review of Cell and Developmental Biology·Margaret Buckingham, Frédéric Relaix
Sep 8, 2016·Thyroid : Official Journal of the American Thyroid Association·Zineb EskalliXavier De Deken
Oct 29, 2014·Nature Reviews. Endocrinology·Lara P FernándezPilar Santisteban
Jun 23, 2011·Endocrinology·Mario De Felice, Roberto Di Lauro

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