{"doi":"10.17615/zpfb-4472","title":"Targeted Inactivation of Mdm2 RING Finger E3 Ubiquitin Ligase Activity in the Mouse Reveals Mechanistic Insights into p53 Regulation","abstract":"It is believed that Mdm2 suppresses p53 in two ways: transcriptional inhibition by direct binding, and degradation via its E3 ligase activity. To study these functions physiologically, we generated mice bearing a single-residue substitution (C462A) abolishing the E3 function without affecting p53 binding. Unexpectedly, homozygous mutant mice died before E7.5, and deletion of p53 rescued the lethality. Furthermore, reintroducing a switchable p53 by crossing with mice surprisingly demonstrated that the mutant Mdm2 was rapidly degraded in a manner indistinguishable from that of the wild-type Mdm2. Hence, our data indicate that (1) the Mdm2-p53 physical interaction, without Mdm2-mediated p53 ubiquitination, cannot control p53 activity sufficiently to allow early mouse embryonic development, and (2) Mdm2's E3 function is not required for Mdm2 degradation.","journal":"UNC Libraries","year":2021,"id":230418,"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":0.9488,"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":254083,"name":"Krishna Bhat","orcid":"0000-0002-2020-8509","position":1,"is_corresponding":false},{"id":393862,"name":"Virginia Godfrey","orcid":null,"position":2,"is_corresponding":false},{"id":32560,"name":"Yanping Zhang","orcid":"0000-0002-1680-7592","position":3,"is_corresponding":false},{"id":574858,"name":"Hua Mao","orcid":"0009-0006-6068-6528","position":4,"is_corresponding":false},{"id":543640,"name":"Hilary V. Clegg","orcid":null,"position":5,"is_corresponding":false},{"id":836126,"name":"Gérard I. Evan","orcid":"0000-0003-0412-1216","position":6,"is_corresponding":false},{"id":541005,"name":"Koji Itahana","orcid":"0000-0002-7241-2894","position":7,"is_corresponding":false},{"id":464542,"name":"Aiwen Jin","orcid":null,"position":8,"is_corresponding":false},{"id":542930,"name":"Yoko Itahana","orcid":"0000-0003-3560-4560","position":9,"is_corresponding":false},{"id":522285,"name":"Mikael S. Lindström","orcid":"0000-0003-1148-8497","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:55:05.844766Z","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":[]}