title: Functional domains of FOXJ2.
abstract: FOXJ2 is a fork head transcriptional activator, the expression of which starts very early in embryonic development and it is distributed widely in the adult. Here, we describe the characterization of domains that are important for its function. FOXJ2 is localized constitutively at the nucleus of the cell. Two tyrosine residues and a stretch of basic amino acid residues at the N and C-terminal ends of the fork head domain, respectively, are important for its nuclear targeting. These residues are conserved strongly among all members of the fork head family, suggesting that they could be involved in the nuclear translocation mechanism of all fork head factors. In addition to the AB domain, we have found, at least, two other transactivation domains: Domain I, at the N terminus, and the H/P domain, rich in histidine and proline residues. Although the AB domain shows the strongest transactivation capacity, all three domains are required for full FOXJ2 transcriptional activity. Furthermore, a fourth region rich in proline and glutamine residues and with no intrinsic transactivation function, the P/Q domain, appears to play an important role in the FOXJ2-mediated transactivation mechanism. Although FOXJ2 can be phosphorylated in two serine residues, this post-translational modification did not appear to be essential for transactivation. Finally, we have found that the W2 wing of the fork head domain of FOXJ2 is dispensable for specific DNA binding, although it could have a weak stabilizing role for the DNA-FOXJ2 complex.
authors.affiliation: Departamento de Biología Celular y Desarrollo, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Velázquez 144, 28006, Madrid, Spain.
authors.forename: María Ana
authors.initials: MA
authors.lastname: Gómez-Ferrería
authors.forename: Javier
authors.initials: J
authors.lastname: Rey-Campos
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors; D049452:Green Fluorescent Proteins; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000378:metabolism
chemical_list: D000596:Amino Acids; D004268:DNA-Binding Proteins; C408469:FOXJ2 protein, human; D051858:Forkhead Transcription Factors; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D004247:DNA