{"doi":"10.1016/j.celrep.2024.114054","title":"14-3-3 binding motif phosphorylation disrupts Hdac4-organized condensates to stimulate cardiac reprogramming","abstract":"Cell fate conversion is associated with extensive post-translational modifications (PTMs) and architectural changes of sub-organelles, yet how these events are interconnected remains unknown. We report here the identification of a phosphorylation code in 14-3-3 binding motifs (PC14-3-3) that greatly stimulates induced cardiomyocyte (iCM) formation from fibroblasts. PC14-3-3 is identified in pivotal functional proteins for iCM reprogramming, including transcription factors and chromatin modifiers. Akt1 kinase and protein phosphatase 2A are the key writer and key eraser of the PC14-3-3 code, respectively. PC14-3-3 activation induces iCM formation with the presence of only Tbx5. In contrast, PC14-3-3 inhibition by mutagenesis or inhibitor-mediated code removal abolishes reprogramming. We discover that key PC14-3-3-embedded factors, such as histone deacetylase 4 (Hdac4), Mef2c, and Foxo1, form Hdac4-organized inhibitory nuclear condensates. PC14-3-3 activation disrupts Hdac4 condensates to promote cardiac gene expression. Our study suggests that sub-organelle dynamics regulated by a PTM code could be a general mechanism for stimulating cell reprogramming.","journal":"Cell Reports","year":2024,"id":433865,"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":13,"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":499047,"name":"Ienglam Lei","orcid":"0000-0002-0248-6871","position":1,"is_corresponding":false},{"id":499048,"name":"Shuo Tian","orcid":"0000-0001-9883-2961","position":2,"is_corresponding":false},{"id":661751,"name":"Wenbin Gao","orcid":"0000-0001-9268-8823","position":3,"is_corresponding":false},{"id":792178,"name":"Yijing Guo","orcid":"0000-0002-6638-8963","position":4,"is_corresponding":false},{"id":792179,"name":"Zhaokai Li","orcid":"0000-0002-3298-1187","position":5,"is_corresponding":false},{"id":1136584,"name":"Ziad Sabry","orcid":"0000-0003-2526-5155","position":6,"is_corresponding":false},{"id":626256,"name":"Paul C. Tang","orcid":"0000-0003-4211-8587","position":7,"is_corresponding":false},{"id":237553,"name":"Y. Eugene Chen","orcid":"0000-0003-2357-7825","position":8,"is_corresponding":false},{"id":499051,"name":"Zhong Wang","orcid":"0000-0002-8720-4609","position":9,"is_corresponding":false},{"id":792177,"name":"Liu Liu","orcid":"0000-0001-8905-1039","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T01:59:49.434790Z","pmid":"38578832","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":[]}