{"doi":"10.1016/j.jbc.2024.107408","title":"Biochemical characterization of the Eya and PP2A-B55α interaction","abstract":"The eyes absent (Eya) proteins were first identified as co-activators of the six homeobox family of transcription factors and are critical in embryonic development. These proteins are also re-expressed in cancers after development is complete, where they drive tumor progression. We have previously shown that the Eya3 N-terminal domain (NTD) contains Ser/Thr phosphatase activity through an interaction with the protein phosphatase 2A (PP2A)-B55α holoenzyme and that this interaction increases the half-life of Myc through pT58 dephosphorylation. Here, we showed that Eya3 directly interacted with the NTD of Myc, recruiting PP2A-B55α to Myc. We also showed that Eya3 increased the Ser/Thr phosphatase activity of PP2A-B55α but not PP2A-B56α. Furthermore, we demonstrated that the NTD (∼250 amino acids) of Eya3 was completely disordered, and it used a 38-residue segment to interact with B55α. In addition, knockdown and phosphoproteomic analyses demonstrated that Eya3 and B55α affected highly similar phosphosite motifs with a preference for Ser/Thr followed by Pro, consistent with Eya3's apparent Ser/Thr phosphatase activity being mediated through its interaction with PP2A-B55α. Intriguingly, mutating this Pro to other amino acids in a Myc peptide dramatically increased dephosphorylation by PP2A. Not surprisingly, Myc P59A , a naturally occurring mutation hotspot in several cancers, enhanced Eya3-PP2A-B55α–mediated dephosphorylation of pT58 on Myc, leading to increased Myc stability and cell proliferation, underscoring the critical role of this phosphosite in regulating Myc stability.","journal":"Journal of Biological Chemistry","year":2024,"id":444712,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1260173,"name":"Ryan Anderson","orcid":"0000-0003-0983-1516","position":1,"is_corresponding":false},{"id":353884,"name":"Lingdi Zhang","orcid":"0000-0002-8671-1385","position":2,"is_corresponding":false},{"id":288136,"name":"Connor J. Hughes","orcid":"0000-0001-6295-8167","position":3,"is_corresponding":false},{"id":769487,"name":"Xueni Li","orcid":"0000-0002-3969-8480","position":4,"is_corresponding":false},{"id":1260650,"name":"Chris Ebmeier","orcid":null,"position":5,"is_corresponding":false},{"id":935214,"name":"Marisa E. Wagley","orcid":null,"position":6,"is_corresponding":false},{"id":480716,"name":"Natalie G. Ahn","orcid":"0000-0002-2690-2630","position":7,"is_corresponding":false},{"id":288139,"name":"Heide L. Ford","orcid":"0000-0002-2860-9841","position":8,"is_corresponding":false},{"id":353890,"name":"Rui Zhao","orcid":"0000-0003-0045-2974","position":9,"is_corresponding":false},{"id":1197653,"name":"Christopher P Alderman","orcid":null,"position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T02:01:37.886033Z","pmid":"38796066","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}