{"doi":"10.1021/jacs.3c04640","title":"Acetylation Targeting Chimera Enables Acetylation of the Tumor Suppressor p53","abstract":"With advances in chemically induced proximity technologies, heterobifunctional modalities such as proteolysis targeting chimeras (PROTACs) have been successfully advanced to clinics for treating cancer. However, pharmacologic activation of tumor-suppressor proteins for cancer treatment remains a major challenge. Here, we present a novel Ace tylation Ta rgeting C himera (AceTAC) strategy to acetylate the p53 tumor suppressor protein. We discovered and characterized the first p53Y220C AceTAC, MS78, which recruits histone acetyltransferase p300/CBP to acetylate the p53Y220C mutant. MS78 effectively acetylated p53Y220C lysine 382 (K382) in a concentration-, time-, and p300-dependent manner and suppressed proliferation and clonogenicity of cancer cells harboring the p53Y220C mutation with little toxicity in cancer cells with wild-type p53. RNA-seq studies revealed novel p53Y220C-dependent upregulation of TRAIL apoptotic genes and downregulation of DNA damage response pathways upon acetylation induced by MS78. Altogether, the AceTAC strategy could provide a generalizable platform for targeting proteins, such as tumor suppressors, via acetylation.","journal":"Journal of the American Chemical Society","year":2023,"id":319502,"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":55,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":3713,"name":"Ning Sun","orcid":"0000-0003-4374-6489","position":1,"is_corresponding":false},{"id":401433,"name":"Xiaoping Hu","orcid":"0000-0001-7014-5983","position":2,"is_corresponding":false},{"id":31291,"name":"Tiphaine Martin","orcid":"0000-0001-9990-1455","position":3,"is_corresponding":false},{"id":1026597,"name":"Jingjie Yi","orcid":"0000-0001-9908-0087","position":4,"is_corresponding":false},{"id":846318,"name":"Yue Zhong","orcid":"0000-0003-2101-8632","position":5,"is_corresponding":false},{"id":305223,"name":"Yan Xiong","orcid":"0000-0003-0676-8267","position":6,"is_corresponding":false},{"id":228876,"name":"H. Ümit Kanıskan","orcid":"0000-0001-5327-832X","position":7,"is_corresponding":false},{"id":106345,"name":"Wei Gu","orcid":"0000-0002-1480-2368","position":8,"is_corresponding":false},{"id":4789,"name":"Ramon Parsons","orcid":"0000-0002-6656-3514","position":9,"is_corresponding":false},{"id":228877,"name":"Jian Jin","orcid":"0000-0002-2387-3862","position":10,"is_corresponding":false},{"id":288995,"name":"Md Kabir","orcid":"0000-0003-1792-2549","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T01:07:12.004111Z","pmid":"37365684","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":[]}