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

Lingdi Zhang | Hengbo Zhou | Xueni Li | Rebecca L Vartuli | Michael Rowse | Yongna Xing | Pratyaydipta Rudra | Debashis Ghosh | Rui Zhao | Heide L Ford
Nature communications | 2018

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)-B55α holoenzyme. Importantly, Eya3 alters the regulation of c-Myc by PP2A, increasing c-Myc stability by enabling PP2A-B55α to dephosphorylate pT58, in direct contrast to the previously described PP2A-B56α-mediated dephosphorylation of pS62 and c-Myc destabilization. Furthermore, Eya3 and PP2A-B55α promote metastasis in a xenograft model of breast cancer, opposing the canonical tumor suppressive function of PP2A-B56α. 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.

Pubmed ID: 29535359

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA095277
  • Agency: NCI NIH HHS, United States
    Id: P30 CA046934
  • Agency: NCI NIH HHS, United States
    Id: R01 CA221282
  • Agency: NCI NIH HHS, United States
    Id: F31 CA189736
  • Agency: NCI NIH HHS, United States
    Id: R21 CA185752
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM096060

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