Figure 9.
A model for the regulation of IGF signaling by p53. (A) Hierarchy of IGF control in normal cells. Major phosphorylation events that occur upon ligand binding are indicated by the “P”s circled in yellow and are connected by green arrows. The pathway bifurcates at Akt/PKB into an FKHR-dependent proliferation branch (right) and a TOR/S6 kinase-dependent anabolic branch (left). p53 exerts several layers of control over the first steps of the cascade (solid red arrows), but also has a fail-safe mechanism of control via p21 late in the cascade (dotted red arrow). (B) Disruption of IGF control by p44. The interaction of p44 with p53 results in permanent activation of the IGF-R, simultaneously triggering growth via the IGF pathway (green arrows) and cell-cycle arrest via Ras (blue arrows).