title: AP-1-mediated expression of brain-specific class IVa β-tubulin in P19 embryonal carcinoma cells.
abstract: Expression of brain-specific phenotypes increased in all trans retinoic acid (ATRA)-induced neural differentiation of mouse P19 embryonal carcinoma cells. Among these phenotypes, expression of class IVa β-tubulin isotype (TUBB4a) was particularly enhanced in neural differentiation. Transient transfection assays employing a reporter construct found that ATRA-mediated regulatory region of the TUBB4a gene lay in the region from -83 nt to +137 nt relative to the +1 transcription start site. Site-directed mutagenesis in the AP-1 binding site at -29/-17 suggested that the AP-1 binding site was a critical region for ATRA-mediated TUBB4a expression. Chromatin immunoprecipitation experiments suggested participation of JunD and activating transcription factor-2 (ATF2) in TUBB4a expression. Additionally, exogenous induction of the dominant-negative (dn) type of JunD canceled ATRA-induced upregulation of TUBB4a, and the dn type of ATF2 suppressed even the basal activity. Further immunoblot study revealed an ATRA-mediated increase in JunD protein, while a significant amount of ATF2 protein was constantly produced. These results suggest that differentiation-mediated activation of JunD results in enhanced TUBB4a expression.
authors: Department of Tissue Physiology, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509, Japan.
authors: Yuka
authors: Y
authors: Maruyama
authors: Kazuhiko
authors: K
authors: Arahara
authors: Emi
authors: E
authors: Kinoshita
authors: Katsuhiko
authors: K
authors: Arai
mesh_terms: D051698:Activating Transcription Factor 2 / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D016297:Mutagenesis, Site-Directed; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism*
chemical_list: D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D017931:DNA Primers; D016755:Proto-Oncogene Proteins c-jun; C000602032:TUBB4A protein, mouse; D018808:Transcription Factor AP-1; D014404:Tubulin; C528955:junD protein, mouse
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