Author Correction: Eya3 partners with PP2A to induce c-Myc stabilization and tumor progression
| Autor: | Heide L. Ford, Lingdi Zhang, Michael Rowse, Hengbo Zhou, Rui Zhao, Pratyaydipta Rudra, Yongna Xing, Rebecca L. Vartuli, Debashis Ghosh, Xueni Li |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Gene knockdown Multidisciplinary business.industry Science General Physics and Astronomy Breast cancer metastasis General Chemistry Protein phosphatase 2 General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 030104 developmental biology Text mining Tumor progression Cancer research Medicine lcsh:Q business lcsh:Science skin and connective tissue diseases |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-1 (2018) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Eya proteins are characterised by phosphatase activity associated with both the evolutionary conserved region and the less conserved N-terminal domain (NTD). Here the authors show that NTD mediates the interaction with PP2A and regulates c-Myc phosphorylation and stability, potentially switching PP2A from a tumour suppressor to an oncogene. |
| Databáze: | OpenAIRE |
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