Fig. 5

Model of Enh^AP1-OIS1 regulation of OIS. a In normal BJ fibroblast cells, hyper-activation of RAS induces MAPK signaling cascade, including AP-1 TFs. Activated AP-1 TFs control different cellular functions, including cell proliferation and apoptosis. AP1 is recruited, among other enhancers, to Enh^AP1-OIS1 and stimulates its activity. This, in turn, promotes the expression of the target gene FOXF1, diverting oncogenic signals into the pre-senescent pathway. b Mutagenesis of the AP-1 binding site in Enh^AP1-OIS1 abrogates its enhancer activity and thus leads to decreased expression of FOXF1. This results in compromised induction of OIS and thus cells continue uncontrolled cell proliferation [52]