In Vivo Role of Different Domains and of Phosphorylation in the Transcription Factor Nkx2-1

Overview

Journal BMC Dev Biol

Publisher Biomed Central

Specialties Biology
Reproductive Medicine

Date 2011 Feb 25

PMID 21345181

Citations 23

Authors

Daniel Silberschmidt

Alina Rodriguez-Mallon

Prathiba Mithboakar

Gaetano Cali

Elena Amendola

Remo Sanges

Mariastella Zannini

Marzia Scarfo

Pasquale De Luca

Lucio Nitsch

Roberto Di Lauro

Mario De Felice

Affiliations

Soon will be listed here.

Abstract

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.

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