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BMC Dev Biol. 2011 Feb 23;11:9. doi: 10.1186/1471-213X-11-9.

In vivo role of different domains and of phosphorylation in the transcription factor Nkx2-1.

Author information

1
Stazione Zoologica Anton Dohrn, Villa Comunale, 80121, Napoli, Italy.

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.

PMID:
21345181
PMCID:
PMC3055846
DOI:
10.1186/1471-213X-11-9
[Indexed for MEDLINE]
Free PMC Article

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