ArticleMolecular and cellular biology2017
EYA1's Conformation Specificity in Dephosphorylating Phosphothreonine in Myc and Its Activity on Myc Stabilization in Breast Cancer.
Article in Molecular and cellular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Adaptive loss of function accelerated the evolution of ancient and modern human cognition.bioRxiv : the preprint server for biology · 2026Article
- MYC Point Mutations in Cancer: A Reboot and a Sequel.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- EYA3 regulation of NF-κB and CCL2 suppresses cytotoxic NK cells in the premetastatic niche to promote TNBC metastasis.Science advances · 2025Article
- Genetic Code Expansion: Recent Developments and Emerging Applications.Chemical reviews · 2025Review
- F-box in breast cancer: mechanism of action and therapeutic potential.American journal of translational research · 2025Review
- Protein phosphatase EYA1 regulates the dephosphorylation and turnover of BCL2L12 to promote glioma development.International journal of biological sciences · 2025Article
- All eyes on Eya: A unique transcriptional co-activator and phosphatase in cancer.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- EYA2 tyrosine phosphatase inhibition reduces MYC and prevents medulloblastoma progression.Neuro-oncology · 2023Article
- Dephosphorylation of Six2Y129 protects tyrosine hydroxylase-positive cells in SNpc by regulating TEA domain 1 expression.iScience · 2023Article
- The transcriptional coactivator Eya1 exerts transcriptional repressive activity by interacting with REST corepressors and REST-binding sequences to maintain nephron progenitor identity.Nucleic acids research · 2022Article
- The Eyes Absent Proteins: Unusual HAD Family Tyrosine Phosphatases.International journal of molecular sciences · 2021Review
- BCOR Binding to MLL-AF9 Is Essential for Leukemia via Altered EYA1, SIX, and MYC Activity.Blood cancer discovery · 2020Article
- The multi-functional eyes absent proteins.Critical reviews in biochemistry and molecular biology · 2020Review
- The Eya1 Phosphatase Mediates Shh-Driven Symmetric Cell Division of Cerebellar Granule Cell Precursors.Developmental neuroscience · 2020Article
- Article
- EYA1 promotes cell migration and tumor metastasis in hepatocellular carcinoma.American journal of translational research · 2019Article
- The impact of phosphatases on proliferative and survival signaling in cancer.Cellular and molecular life sciences : CMLS · 2018Review
- Eya3 promotes breast tumor-associated immune suppression via threonine phosphatase-mediated PD-L1 upregulation.The Journal of clinical investigation · 2018Article
- Eya3 partners with PP2A to induce c-Myc stabilization and tumor progression.Nature communications · 2018Article
- The Eya phosphatase: Its unique role in cancer.The international journal of biochemistry & cell biology · 2018Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
EYA1 is known to be overexpressed in human breast cancer, in which the Myc protein is also accumulated in association with decreased phospho-T58 (pT58) levels. We have recently reported that EYA1 functions as a unique protein phosphatase to dephosphorylate Myc at pT58 to regulate Myc levels. However, it remains unclear whether EYA1-mediated Myc dephosphorylation on T58 is a critical function in regulating Myc protein stability in breast cancer. Furthermore, EYA1's substrate specificity has remained elusive. In this study, we have investigated these questions, and here, we report that depletion of EYA1 using short hairpin RNA (shRNA) in breast cancer cells destabilizes the Myc protein and increases pT58 levels, leading to an increase in the doubling time and impairment of cell cycle progression. In correlation with EYA1-mediated stabilization of cMyc and reduced levels of pT58, EYA1 greatly reduced cMyc-FBW7 binding and cMyc ubiquitination, thus providing novel insight into how EYA1 acts to regulate the FBW7-mediated Myc degradation machinery. We found that the conserved C-terminal haloacid dehalogenase domain of EYA1, which has been reported to have only tyrosine phosphatase activity, has dual phosphatase activities, and both the N- and C-terminal domains interact with substrates to increase the catalytic activity of EYA1. Enzymatic assay and nuclear magnetic resonance (NMR) analysis demonstrated that EYA1 has a striking conformation preference for phospho-T58 of Myc. Together, our results not only provide novel structural evidence about the conformation specificity of EYA1 in dephosphorylating phosphothreonine in Myc but also reveal an important mechanism contributing to Myc deregulation in human breast cancer.
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