{"doi":"10.1042/bcj20240726","title":"Aurora A binds to the transactivation domain of c-Myc and recognizes the phosphorylated N-terminal degron motif","abstract":"The oncoprotein c-Myc is overexpressed or mutated in a large fraction of human cancers. The stability of c-Myc is controlled by phosphorylation of T58 and S62 within a conserved degron motif in the N-terminal transactivation domain, which triggers recruitment of the SCF ubiquitin ligase. The kinase Aurora A (AurA) has been shown to bind to both c-Myc and its paralog N-Myc and to promote their stability by interfering with ubiquitination and degradation. Here we show, using NMR and FRET experiments, that AurA binds to c-Myc through several discrete interactions spanning 145 residues within its transactivation domain. AurA binding to c-Myc is enhanced by phosphorylation of the T58/S62 degron, demonstrating that the kinase recognizes the pool of c-Myc that has been marked for degradation by the ubiquitin proteasome pathway. Although AurA binds to segments of c-Myc flanking the degron, it does not appear to form extensive interactions with the phosphorylated degron itself, potentially leaving it accessible on the AurA surface. These observations establish a foundation for understanding the role of AurA in regulating c-Myc ubiquitination and degradation.","journal":"Biochemical Journal","year":2025,"id":543610,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9494,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1104741,"name":"Katie Dunleavy","orcid":null,"position":1,"is_corresponding":false},{"id":1433627,"name":"Kaitlin Beel","orcid":null,"position":2,"is_corresponding":false},{"id":649132,"name":"Tiffany A. Engel","orcid":null,"position":3,"is_corresponding":false},{"id":1433182,"name":"Andrew R. Thompson","orcid":"0000-0001-6788-7222","position":4,"is_corresponding":false},{"id":1433628,"name":"Felix L. John","orcid":null,"position":5,"is_corresponding":false},{"id":417547,"name":"David D. Thomas","orcid":"0000-0002-8822-2040","position":6,"is_corresponding":false},{"id":648490,"name":"Nicholas M. Levinson","orcid":"0000-0003-4338-8087","position":7,"is_corresponding":false},{"id":1433181,"name":"Nidhi Joshi","orcid":"0000-0001-7751-1181","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T02:53:04.088079Z","pmid":"40178520","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":[]}