Lactosylceramide (Lac-Cer) constitutes the backbone structure of various gangliosides whose abnormal expression is associated with malignancy of neuroblastoma. The understanding of the regulatory mechanism of Lac-Cer contributes to the development of neuroblastoma therapy. In this study, the transcriptional mechanism of mouse β4-galactosyltransferase (β4GalT) 6, which is one of Lac-Cer synthase, was analyzed using mouse neuroblastoma cell line Neuro-2a. The -226 to -13 region relative to the most downstream transcriptional start site was determined to be the promoter region by luciferase assay using the 5'-deletion constructs. The mutation into the activating protein (AP) 4-binding site -110/-101 drastically decreased the promoter activity, indicating that this site is mainly implicated in the transcription. Furthermore, the mutation into the GATA-binding site -210/-201 or another AP4-binding site -202/-193 partially decreased the promoter activity. The study suggests that the mouse β4GalT6 gene is transcriptionally regulated by AP4 in cooperation with GATA family transcription factor in neuroblastoma.
Keywords: GATA; activating protein (AP) 4; neuroblastoma; transcriptional mechanism; β4-galactosyltransferase 6.