AP-1-Mediated Expression of Brain-Specific Class IVa β-Tubulin in P19Embryonal Carcinoma Cells

[摘要] References(36)Cited-By(1)Supplementary materials(1)Expression of brain-specificphenotypes increased in all trans retinoic acid (ATRA)-induced neuraldifferentiation of mouse P19 embryonal carcinoma cells. Among these phenotypes, expressionof class IVa β-tubulin isotype (TUBB4a) was particularly enhanced in neuraldifferentiation. Transient transfection assays employing a reporter construct found thatATRA-mediated regulatory region of the TUBB4a gene lay in the region from �?83 nt to +137nt relative to the +1 transcription start site. Site-directed mutagenesis in the AP-1binding site at �?29/�?17 suggested that the AP-1 binding site was a critical region forATRA-mediated TUBB4a expression. Chromatin immunoprecipitation experiments suggestedparticipation of JunD and activating transcription factor-2 (ATF2) in TUBB4a expression.Additionally, exogenous induction of the dominant-negative (dn) type of JunD canceledATRA-induced upregulation of TUBB4a, and the dn type of ATF2 suppressed even the basalactivity. Further immunoblot study revealed an ATRA-mediated increase in JunD protein,while a significant amount of ATF2 protein was constantly produced. These results suggestthat differentiation-mediated activation of JunD results in enhanced TUBB4aexpression.

[学科分类] 兽医学

[关键词] embryonal carcinoma cell;neuronal differentiation;promoter analysis;retinoic acid;tubulin isotype