{"doi":"10.1073/pnas.260501497","title":"Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to histone deacetylase 5","abstract":"<jats:p>Skeletal muscle differentiation is controlled by interactions\n between myocyte enhancer factor-2 (MEF2) and myogenic basic\n helix—loop–helix transcription factors. Association of MEF2 with\n histone deacetylases (HDAC) -4 and -5 results in repression of MEF2\n target genes and inhibition of myogenesis.\n Calcium/calmodulin-dependent protein kinase (CaMK)\n signaling promotes myogenesis by disrupting MEF2–HDAC complexes and\n stimulating HDAC nuclear export. To further define the mechanisms that\n confer CaMK responsiveness to HDAC4 and -5, we performed yeast\n two-hybrid screens to identify HDAC-interacting factors. These screens\n revealed interactions between HDAC4 and members of the 14-3-3 family of\n proteins, which function as signal-dependent intracellular chaperones.\n HDAC4 binds constitutively to 14-3-3 in yeast and mammalian cells,\n whereas HDAC5 binding to 14-3-3 is largely dependent on CaMK signaling.\n CaMK phosphorylates serines -259 and -498 in HDAC5, which subsequently\n serve as docking sites for 14-3-3. Our studies suggest that 14-3-3\n binding to HDAC5 is required for CaMK-dependent disruption of\n MEF2–HDAC complexes and nuclear export of HDAC5, and implicate 14-3-3\n as a signal-dependent regulator of muscle cell differentiation.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2000,"id":663889,"datarank":13.165351955868873,"base_score":6.269096283706261,"endowment":6.269096283706261,"self_citation_contribution":0.9403644425559393,"citation_network_contribution":12.224987513312934,"self_endowment_contribution":0.9403644425559393,"citer_contribution":12.224987513312934,"corpus_percentile":null,"corpus_rank":null,"citation_count":527,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1729970,"name":"Chun Li Zhang","orcid":null,"position":1,"is_corresponding":false},{"id":225271,"name":"Eric N. Olson","orcid":"0000-0003-1151-8262","position":2,"is_corresponding":false},{"id":45204,"name":"Timothy A. McKinsey","orcid":"0000-0001-7778-4470","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to histone deacetylase 5","abstract":"<jats:p>Skeletal muscle differentiation is controlled by interactions\n between myocyte enhancer factor-2 (MEF2) and myogenic basic\n helix—loop–helix transcription factors. Association of MEF2 with\n histone deacetylases (HDAC) -4 and -5 results in repression of MEF2\n target genes and inhibition of myogenesis.\n Calcium/calmodulin-dependent protein kinase (CaMK)\n signaling promotes myogenesis by disrupting MEF2–HDAC complexes and\n stimulating HDAC nuclear export. To further define the mechanisms that\n confer CaMK responsiveness to HDAC4 and -5, we performed yeast\n two-hybrid screens to identify HDAC-interacting factors. These screens\n revealed interactions between HDAC4 and members of the 14-3-3 family of\n proteins, which function as signal-dependent intracellular chaperones.\n HDAC4 binds constitutively to 14-3-3 in yeast and mammalian cells,\n whereas HDAC5 binding to 14-3-3 is largely dependent on CaMK signaling.\n CaMK phosphorylates serines -259 and -498 in HDAC5, which subsequently\n serve as docking sites for 14-3-3. Our studies suggest that 14-3-3\n binding to HDAC5 is required for CaMK-dependent disruption of\n MEF2–HDAC complexes and nuclear export of HDAC5, and implicate 14-3-3\n as a signal-dependent regulator of muscle cell differentiation.</jats:p>","is_dataset_classified":null,"base_score":6.269096283706261,"endowment":6.269096283706261,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"11114197","pmcid":"PMC18930","openalex_id":"https://openalex.org/W2154572495","authors":[],"funders":[],"total_grants":0,"fwci":10.064,"citation_percentile":0.98877682,"influential_citations":0,"citation_trend":[{"year":2012,"count":20},{"year":2013,"count":26},{"year":2014,"count":24},{"year":2015,"count":21},{"year":2016,"count":18},{"year":2017,"count":18},{"year":2018,"count":13},{"year":2019,"count":10},{"year":2020,"count":17},{"year":2021,"count":13},{"year":2022,"count":11},{"year":2023,"count":7},{"year":2024,"count":18},{"year":2025,"count":14},{"year":2026,"count":6}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://pnas.org/doi/pdf/10.1073/pnas.260501497","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.260501497","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11114197","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/18930","host_type":"repository"}],"fields_of_study":["14-3-3 protein interactions","Ubiquitin and proteasome pathways","Histone Deacetylase Inhibitors Research"],"mesh_terms":["Animals","Binding Sites","Biological Transport","Cell Nucleus","Chlorocebus aethiops","DNA-Binding Proteins","Histone Deacetylases","Repressor Proteins","Saccharomyces cerevisiae","Serine","Transcription Factors","Tyrosine 3-Monooxygenase","Signal Transduction","Calcium-Calmodulin-Dependent Protein Kinases","Myogenic Regulatory Factors","COS Cells","14-3-3 Proteins","Mice","MEF2 Transcription Factors"],"keywords":["Mef2","Histone deacetylase 5","HDAC4","CAMK","Biology","Transcription factor","Cell biology","Histone deacetylase","Calmodulin","Myogenic regulatory factors","Myogenesis","Enhancer","Signal transduction","Histone","Protein kinase A","Myocyte","Kinase","Biochemistry","MyoD","Autophosphorylation"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-13T00:03:18.007881Z","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":[]}