Figure 5.

Disrupting Myc stability: (A) In cancer, PI3K signaling inactivates GSK3, preventing phosphorylation of T58 Myc. Pin1 overexpression keeps Myc in the cis-confirmation, preventing PP2A trans-specific enzyme from binding to Myc. Furthermore, PP2A is inactivated in several cancers, and therefore S62 remains phosphorylated. All of this leads to high Myc stability. (B) Inhibition of PI3K allows for GSK3 to phosphorylate T58 on Myc, which is required for degradation. Pin1 inhibitors and PP2A activators allow for PP2A to recognize and remove the phosphorylation of S62, leading to low stability and Myc’s degradation.