FIGURE 6. Model of Snail transcriptional regulation by PARP-1 and effect of the differential Snail expression on apoptosis in MDA-MB-231 cells.

The presence or absence of PARP-1 on the SNAI1 promoter/enhancer, which depends on the rate of PARP activity, affects the activity of SNAI1 promoter (see Discussion). After the doxorubicin treatment (left side), PARP activity increases and PARP-1 detaches from DNA probably bringing away repressive factors (gray circle) from the promoter while other positive transcription factors (blue circles) may bind it. This event causes a strong increase in Snail transcription (green circles) and the consequent repression of its target gene PTEN which results in resistance to apoptosis. After the treatment with doxo/ABT-888 (right side), PARP activity decreases and PARP-1 can bind the SNAI1 promoter/enhancer possibly causing the release of positive transcription factors from the promoter (light blue circles). The Snail transcription is lower, leading to a less efficacious repression of Snail on PTEN transcription and to a significant recovery of the apoptotic process.