AP-2 enhances Sp1-dependent activation of the growth-regulated human ATP/ADP translocator

The mammalian ATP/ADP translocator isoform-2 (ANT2) gene is growth-activated. Regulation of the gene appears to involve Sp1, as an essential activator, and a suppressor through an Sp1 core element next to the transcription start. We show here that the proximal promoter also binds AP-2 strongly and specifically to two sites, one of which overlaps the Sp1 proximal suppressor site. AP-2 binds with an affinity of 10 to15 fold higher than that of Sp1. AP-2 alone does not alter the ANT2 promoter activity in transfected SL2 cells, but enhances the Sp1-dependent activation of the promoter several fold. Enhancement by AP-2 is observed only when Sp1 is limiting for transcription activation. These data suggest that the cellular AP-2/Sp1 ratio might influence ANT2 expression in developing or differentiating cells.