EDC3 Phosphorylation Regulates Tumor Growth and Invasion Through Controlling Modifications in P-body Formation and Dynamics.

Regulation of mRNA stability and translation plays a critical role in determining protein abundance within cells. Processing bodies are critical regulators of these processes. We report that the Pim1 protein kinase binds to the internally disordered region of a core P-body component EDC3, enhancer of mRNA-decapping protein 3, inducing the phosphorylation of EDC3 on serine 161 which significantly modifies P-body activity and content. This phosphorylation is highly elevated in a large number of tumor cell types and prevents the localization of EDC3 to P-bodies. RNAs isolated from purified P-bodies using a unique methodology contain approximately seven thousand differentially distributed mRNAs compared to whole-cells. Treatment with protein kinase inhibitors alters approximately 4 percent of the translatable mRNAs elevating specific 5 prime sequences within P-bodies. Genome edited cells harboring the S161 to alanine mutation mimic a dephosphorylated state and block tumor cell migration and invasion, and dramatically suppress tumor growth in tissue culture and mouse xenograft models. These results demonstrate that EDC3 phosphorylation regulates multiple biological functions and the modulation of the specific mRNA content of P-bodies.