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In vivo role of different domains and of phosphorylation in the transcription factor Nkx2-1
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 phosphorylat...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055846/ https://www.ncbi.nlm.nih.gov/pubmed/21345181 http://dx.doi.org/10.1186/1471-213X-11-9 |
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author | Silberschmidt, Daniel Rodriguez-Mallon, Alina Mithboakar, Prathiba Calì, Gaetano Amendola, Elena Sanges, Remo Zannini, Mariastella Scarfò, Marzia De Luca, Pasquale Nitsch, Lucio Di Lauro, Roberto De Felice, Mario |
author_facet | Silberschmidt, Daniel Rodriguez-Mallon, Alina Mithboakar, Prathiba Calì, Gaetano Amendola, Elena Sanges, Remo Zannini, Mariastella Scarfò, Marzia De Luca, Pasquale Nitsch, Lucio Di Lauro, Roberto De Felice, Mario |
author_sort | Silberschmidt, Daniel |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-3055846 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-30558462011-03-12 In vivo role of different domains and of phosphorylation in the transcription factor Nkx2-1 Silberschmidt, Daniel Rodriguez-Mallon, Alina Mithboakar, Prathiba Calì, Gaetano Amendola, Elena Sanges, Remo Zannini, Mariastella Scarfò, Marzia De Luca, Pasquale Nitsch, Lucio Di Lauro, Roberto De Felice, Mario BMC Dev Biol Research Article 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. BioMed Central 2011-02-23 /pmc/articles/PMC3055846/ /pubmed/21345181 http://dx.doi.org/10.1186/1471-213X-11-9 Text en Copyright ©2011 Silberschmidt et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Silberschmidt, Daniel Rodriguez-Mallon, Alina Mithboakar, Prathiba Calì, Gaetano Amendola, Elena Sanges, Remo Zannini, Mariastella Scarfò, Marzia De Luca, Pasquale Nitsch, Lucio Di Lauro, Roberto De Felice, Mario In vivo role of different domains and of phosphorylation in the transcription factor Nkx2-1 |
title | In vivo role of different domains and of phosphorylation in the transcription factor Nkx2-1 |
title_full | In vivo role of different domains and of phosphorylation in the transcription factor Nkx2-1 |
title_fullStr | In vivo role of different domains and of phosphorylation in the transcription factor Nkx2-1 |
title_full_unstemmed | In vivo role of different domains and of phosphorylation in the transcription factor Nkx2-1 |
title_short | In vivo role of different domains and of phosphorylation in the transcription factor Nkx2-1 |
title_sort | in vivo role of different domains and of phosphorylation in the transcription factor nkx2-1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055846/ https://www.ncbi.nlm.nih.gov/pubmed/21345181 http://dx.doi.org/10.1186/1471-213X-11-9 |
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