{"doi":"10.17615/dseb-ee30","title":"Regulation of p53 by Mdm2 E3 Ligase Function Is Dispensable in Embryogenesis and Development, but Essential in Response to DNA Damage","abstract":"Mdm2 E3 ubiquitin ligase-mediated p53 degradation is generally accepted as the major mechanism for p53 regulation; nevertheless, the in vivo significance of this function has not been unequivocally established. Here, we have generated an Mdm2Y487A knock-in mouse; Mdm2Y487A mutation inactivates Mdm2 E3 ligase function without affecting its ability to bind its homologue MdmX. Unexpectedly, Mdm2Y487A/Y487A mice were viable and developed normally into adulthood. While disruption of Mdm2 E3 ligase function resulted in p53 accumulation, p53 transcriptional activity remained low; however, exposure to sub-lethal stress resulted in hyperactive p53 and p53-dependent mortality in Mdm2Y487A/Y487A mice. These findings reveal a potentially dispensable nature for Mdm2 E3 ligase function in p53 regulation, providing insight that may affect how this pathway is targeted therapeutically.","journal":"UNC Libraries","year":2020,"id":144298,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9474,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":464542,"name":"Aiwen Jin","orcid":null,"position":1,"is_corresponding":false},{"id":543639,"name":"Laura A. Tollini","orcid":null,"position":2,"is_corresponding":false},{"id":32560,"name":"Yanping Zhang","orcid":"0000-0002-1680-7592","position":3,"is_corresponding":false},{"id":613357,"name":"Jikyoung Park","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:45.339291Z","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":[]}