title: In vivo role of different domains and of phosphorylation in the transcription factor Nkx2-1.
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.
authors.affiliation: Stazione Zoologica Anton Dohrn, Villa Comunale, 80121, Napoli, Italy.
authors.forename: Daniel
authors.initials: D
authors.lastname: Silberschmidt
authors.forename: Alina
authors.initials: A
authors.lastname: Rodriguez-Mallon
authors.forename: Prathiba
authors.initials: P
authors.lastname: Mithboakar
authors.forename: Gaetano
authors.initials: G
authors.lastname: Calì
authors.forename: Elena
authors.initials: E
authors.lastname: Amendola
authors.forename: Remo
authors.initials: R
authors.lastname: Sanges
authors.forename: Mariastella
authors.initials: M
authors.lastname: Zannini
authors.forename: Marzia
authors.initials: M
authors.lastname: Scarfò
authors.forename: Pasquale
authors.initials: P
authors.lastname: De Luca
authors.forename: Lucio
authors.initials: L
authors.lastname: Nitsch
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Lauro
authors.forename: Mario
authors.initials: M
authors.lastname: De Felice
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D055879:Gene Knock-In Techniques; D055786:Gene Knockout Techniques; D005838:Genotype; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D010766:Phosphorylation; D010902:Pituitary Gland / Q000196:embryology*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary / Q000235:genetics; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D013961:Thyroid Gland / Q000002:abnormalities / Q000196:embryology*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors