Background: The transcription factor Nkx2-1 (also known as TTF-1, Titf1 or T/EBP) contains two apparently redundant activation domains and is post-translationally modified by phosphorylation. We have generated mouse mutant strains to assess the roles of the two activation domains and of phosphorylation in mouse development and differentiation. Results: Mouse strains expressing variants of the transcription factor Nkx2-1 deleted of either activation domain have been constructed. Phenotypic analysis shows for each mutant a distinct set of defects demonstrating that distinct portions of the protein endow diverse developmental functions of Nkx2-1. Furthermore, a mouse strain expressing a Nkx2-1 protein mutated in the phosphorylation sites shows a thyroid gland with deranged follicular organization and gene expression profile demonstrating the functional role of phosphorylation in Nkx2-1. Conclusions: The pleiotropic functions of Nkx2-1 are not all due to the protein as a whole since some of them can be assigned to separate domains of the protein or to specific post-translational modifications. These results have implication for the evolutionary role of mutations in transcription factors. Â© 2011 Silberschmidt et al; licensee BioMed Central Ltd.
|Titolo:||In vivo role of different domains and of phosphorylation in the transcription factor Nkx2-1|
|Autori:||Silberschmidt, Daniel; Rodriguez-Mallon, Alina; Mithboakar, Prathiba; Cal, Gaetano; Amendola, Elena; Sanges, Remo; Zannini, Mariastella; Scarf, Marzia; De Luca, Pasquale; Nitsch, Lucio; Di Lauro, Roberto; De Felice, Mario|
|Data di pubblicazione:||2011|
|Numero di Articolo:||9|
|Digital Object Identifier (DOI):||10.1186/1471-213X-11-9|
|Appare nelle tipologie:||1.1 Journal article|