{"doi":"10.1016/j.celrep.2024.114510","title":"Proteomic analysis reveals a PLK1-dependent G2/M degradation program and a role for AKAP2 in coordinating the mitotic cytoskeleton","abstract":"Ubiquitination is an essential regulator of cell division. The kinase Polo-like kinase 1 (PLK1) promotes protein degradation at G2/M phase through the E3 ubiquitin ligase Skp1-Cul1-F box (SCF) βTrCP . However, the magnitude to which PLK1 shapes the mitotic proteome is uncharacterized. Combining quantitative proteomics with pharmacologic PLK1 inhibition revealed a widespread, PLK1-dependent program of protein breakdown at G2/M. We validated many PLK1-regulated proteins, including substrates of the cell-cycle E3 SCF Cyclin F , demonstrating that PLK1 promotes proteolysis through at least two distinct E3 ligases. We show that the protein-kinase-A-anchoring protein A-kinase anchor protein 2 (AKAP2) is cell-cycle regulated and that its mitotic degradation is dependent on the PLK1/βTrCP signaling axis. Expression of a non-degradable AKAP2 mutant resulted in actin defects and aberrant mitotic spindles, suggesting that AKAP2 degradation coordinates cytoskeletal organization during mitosis. These findings uncover PLK1's far-reaching role in shaping the mitotic proteome post-translationally and have potential implications in malignancies where PLK1 is upregulated.","journal":"Cell Reports","year":2024,"id":428624,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9565,"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":304000,"name":"Kimberly Lukasik","orcid":"0000-0002-2565-0275","position":1,"is_corresponding":false},{"id":843228,"name":"Carolyn Hsu","orcid":null,"position":2,"is_corresponding":false},{"id":269566,"name":"Thomas Bonacci","orcid":null,"position":3,"is_corresponding":false},{"id":368387,"name":"Derek L. Bolhuis","orcid":"0000-0002-9062-9739","position":4,"is_corresponding":false},{"id":368386,"name":"Xianxi Wang","orcid":"0000-0001-5768-881X","position":5,"is_corresponding":false},{"id":430588,"name":"Christine A. Mills","orcid":"0000-0003-0372-4154","position":6,"is_corresponding":false},{"id":1178185,"name":"E Drew Toomer","orcid":null,"position":7,"is_corresponding":false},{"id":1178186,"name":"Owen G Canterbury","orcid":null,"position":8,"is_corresponding":false},{"id":549405,"name":"Kevin Robertson","orcid":null,"position":9,"is_corresponding":false},{"id":347850,"name":"Timothy B. Branigan","orcid":"0000-0002-8641-5332","position":10,"is_corresponding":false},{"id":241659,"name":"Nicholas G. Brown","orcid":"0000-0002-6141-0164","position":11,"is_corresponding":false},{"id":397771,"name":"Laura E. Herring","orcid":"0000-0003-4496-7312","position":12,"is_corresponding":false},{"id":326425,"name":"Stephanie L. Gupton","orcid":"0000-0003-0087-5432","position":13,"is_corresponding":false},{"id":268429,"name":"Michael J. Emanuele","orcid":"0000-0003-4104-7449","position":14,"is_corresponding":false},{"id":298870,"name":"Ryan D. Mouery","orcid":"0000-0002-1866-1742","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-19T01:59:02.165535Z","pmid":"39018246","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":[]}