An inhibitor of Sp1 (mithramycin-a) dose-dependently blocks NGF and Sp1- dependent P2-promoter activity in PC12 cells. P2-promoter reporter plasmid (0.4 kb) directs an ~2 fold increase in luciferase activity when treated with NGF × 48 hours . Treatment with an inhibitor (mithramycin-a) of Sp1 function that disrupts GC-box/transcription factor binding, blocked the NGF-dependent P2-promoter activity. When the experiment was repeated in the presence of co-transfected Sp1, the expected increase in activity directed by Sp1 was dose-dependently inhibited by mithramycin-a. Error bars SEM (n = 3) triplicate measures. Significant differences: ANOVA (***) p < 0.001, (*) p < 0.05.