Figure 4.

E2F1 is involved in crosstalk with Ras–Raf–MEK–ERK and PI3K–AKT pathways. E2F1 promotes sustained AKT activation through Gab2, whereas AKT in turn inhibits E2F1-mediated apoptosis by activation of TopBP1. ERK1/2 is known to upregulate the expression of cyclin D1,⁵¹ which induces the activation of CDK4/6 and subsequently phosphorylates pRB to release E2F1. Meanwhile, E2F1 also regulates ERK activation via transactivation of RasGRP1 and RasGEF1B, which positively affects Ras activity. Thus E2F1 induces two positive feedback loops for survival