{"doi":"10.1101/2021.03.02.433577","title":"PP2A/B55α substrate recruitment as defined by the retinoblastoma-related protein p107","abstract":"Abstract Protein phosphorylation is a reversible post-translation modification essential in cell signaling. This study addresses a long-standing question as to how the most abundant serine/threonine Protein Phosphatase 2 (PP2A) holoenzyme, PP2A/B55α, specifically recognizes substrates and presents them to the enzyme active site. Here, we show how the PP2A regulatory subunit B55α recruits p107, a pRB-related tumor suppressor and B55α substrate. Using molecular and cellular approaches, we identified a conserved region 1 (R1, residues 615-626) encompassing the strongest p107 binding site. This enabled us to identify an “HxRVxxV 619-625 ” short linear motif (SLiM) in p107 as necessary for B55α binding and dephosphorylation of the proximal pSer-615 in vitro and in cells. Numerous B55α/PP2A substrates, including TAU, contain a related SLiM C-terminal from a proximal phosphosite, “ p [ ST ]- P- x(5-10)-[ RK ]- V -x-x-[ VI ]- R ”. Mutation of conserved SLiM residues in TAU dramatically inhibits dephosphorylation by PP2A/B55α, validating its generality. A data-guided computational model details the interaction of residues from the conserved p107 SLiM, the B55α groove, and phosphosite presentation. Altogether these data provide key insights into PP2A/B55α mechanisms of substrate recruitment and active site engagement, and also facilitate identification and validation of new substrates, a key step towards understanding PP2A/B55〈 role in multiple cellular processes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":216440,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":363455,"name":"Ziran Zhao","orcid":"0000-0002-8349-5322","position":1,"is_corresponding":false},{"id":307352,"name":"Qifang Xu","orcid":"0000-0002-1606-7045","position":2,"is_corresponding":false},{"id":345392,"name":"Xinru Wang","orcid":"0000-0001-5994-707X","position":3,"is_corresponding":false},{"id":812831,"name":"Mary Adeyemi","orcid":null,"position":4,"is_corresponding":false},{"id":812832,"name":"Felicity Feiser","orcid":null,"position":5,"is_corresponding":false},{"id":485100,"name":"Alison Kurimchak","orcid":"0000-0003-2608-0128","position":6,"is_corresponding":false},{"id":273955,"name":"Arminja N. Kettenbach","orcid":"0000-0003-3979-4576","position":7,"is_corresponding":false},{"id":345395,"name":"Rebecca Page","orcid":"0000-0002-4645-1232","position":8,"is_corresponding":false},{"id":303861,"name":"Wolfgang Peti","orcid":"0000-0002-8830-6594","position":9,"is_corresponding":false},{"id":56679,"name":"Roland L. Dunbrack","orcid":"0000-0001-7674-6667","position":10,"is_corresponding":false},{"id":363460,"name":"Xavier Graña","orcid":"0000-0001-7134-0473","position":11,"is_corresponding":false},{"id":365230,"name":"Holly Fowle","orcid":null,"position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-18T23:53:11.245932Z","pmid":null,"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":[]}