FIGURE 6.

The results of PEDF-driven Erk5 activation. A, PEDF exposure causes sequential activation of MEK5 and Erk5, which leads to PPARγ activation followed by NFκB activation, endothelial cell apoptosis, and anti-angiogenesis. B, proposed mechanism of PPARγ-dependent induction of NFκB expression. PPARγ/RXR heterodimers recruit SMRT to the p65/RelA promoter: SMRT, in turn, recruits HDAC1, which causes transcriptional repression. When phosphorylated by PEDF, Erk5 displaces SMRT, and thus releases HDAC1 and alleviates trans-repression by PPARγ.