Phosphorylation is the switch that turns PEA-15 from tumor suppressor to tumor promoter

Abstract

Abnormal ERK signaling is implicated in many human diseases including cancer. This signaling cascade is a good target for the therapy of certain malignancies because of its important role in regulating cell proliferation and survival. The small phosphoprotein PEA-15 is a potent regulator of the ERK signaling cascade, and by acting on this pathway, has been described to have both tumor-suppressor and tumorpromoter functions. However, the exact mechanism by which PEA-15 drives the outcome one way or the other remains unclear. We propose that the cellular environment is crucial in determining PEA-15 protein function by affecting the protein's phosphorylation state. We hypothesize that only unphosphorylated PEA-15 can act as a tumor-suppressor and that phosphorylation alters the interaction with binding partners to promote tumor development. In order to use PEA- 15 as a prognostic marker or therapeutic target it is therefore important to evaluate its phosphorylation status. © 2012 Landes Bioscience.