Eya3 partners with PP2A to induce c-Myc stabilization and tumor progression.

ABSTRACT: Eya genes encode a unique family of multifunctional proteins that serve as transcriptional co-activators and as haloacid dehalogenase-family Tyr phosphatases. Intriguingly, the N-terminal domain of Eyas, which does not share sequence similarity to any known phosphatases, contains a separable Ser/Thr phosphatase activity. Here, we demonstrate that the Ser/Thr phosphatase activity of Eya is not intrinsic, but arises from its direct interaction with the protein phosphatase 2A (PP2A)-B55? holoenzyme. Importantly, Eya3 alters the regulation of c-Myc by PP2A, increasing c-Myc stability by enabling PP2A-B55? to dephosphorylate pT58, in direct contrast to the previously described PP2A-B56?-mediated dephosphorylation of pS62 and c-Myc destabilization. Furthermore, Eya3 and PP2A-B55? promote metastasis in a xenograft model of breast cancer, opposing the canonical tumor suppressive function of PP2A-B56?. Our study identifies Eya3 as a regulator of PP2A, a major cellular Ser/Thr phosphatase, and uncovers a mechanism of controlling the stability of a critical oncogene, c-Myc.

SUBMITTER: Zhang L 

PROVIDER: S-EPMC5849647 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature