{"doi":"10.1677/jme.0.0320481","title":"The enhancement of nuclear receptor transcriptional activation by a mouse actin-binding protein, alpha actinin 2","abstract":"<jats:p>The p160 coactivators, steroid receptor coactivator 1, glucocorticoid receptor interacting protein 1 (GRIP1) and the activator of thyroid and retinoic acid receptor, have two activation domains, AD1 and AD2, which transmit the activation signal from the DNA-bound nuclear receptor to the chromatin and/or transcription machinery. In screening for mammalian proteins that bind the AD2 of GRIP1, we identified a mouse actin-binding protein, alpha actinin 2 (mACTN2). mACTN2 was expressed in the heart, skeletal muscle, lung, brain and testis, but there was no expression in the spleen, liver or kidney. Interestingly, the expression level of mACTN2 in the developing embryo depended on the embryonic stage. We further demonstrated that mACTN2 could enhance two transactivation activities of GRIP1, which in turn could enhance the homodimerization of mACTN2. Importantly, mACTN2 not only served as a primary coactivator for androgen receptor, estrogen receptor and thyroid receptor activities, but also acted synergistically with GRIP1 to enhance these nuclear receptor (NR) functions. However, the NR binding motif, LXXLL, conserved in mACTN2 and other actinin family proteins, might be a dispensable domain for its coactivator roles in NRs. These findings suggested that mACTN2 might play an important role in GRIP1-induced NR coactivator functions.</jats:p>","journal":"Journal of Molecular Endocrinology","year":2004,"id":24350,"datarank":2.470557142742789,"base_score":3.8066624897703196,"endowment":3.8066624897703196,"self_citation_contribution":0.5709993734655481,"citation_network_contribution":1.899557769277241,"self_endowment_contribution":0.5709993734655481,"citer_contribution":1.899557769277241,"corpus_percentile":null,"corpus_rank":null,"citation_count":44,"citer_count":44,"citers_with_citation_signal":37,"citers_with_endowment":37,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":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":146382,"name":"CJ Huang","orcid":null,"position":1,"is_corresponding":false},{"id":146383,"name":"WM Wang","orcid":null,"position":2,"is_corresponding":false},{"id":146384,"name":"JC Kang","orcid":null,"position":3,"is_corresponding":false},{"id":146385,"name":"WC Hsu","orcid":null,"position":4,"is_corresponding":false},{"id":146381,"name":"SM Huang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.8066624897703196,"endowment":3.8066624897703196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"15072553","pmcid":null,"openalex_id":"https://openalex.org/W2157632679","authors":[],"funders":[],"total_grants":0,"fwci":2.5386,"citation_percentile":0.89353212,"influential_citations":1,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":1},{"year":2014,"count":4},{"year":2015,"count":4},{"year":2017,"count":1},{"year":2019,"count":1},{"year":2020,"count":2},{"year":2021,"count":3},{"year":2023,"count":1},{"year":2024,"count":1},{"year":2025,"count":2}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://jme.bioscientifica.com/downloadpdf/journals/jme/32/2/481.pdf","host_type":"journal"},{"url":"https://jme.bioscientifica.com/downloadpdf/journals/jme/32/2/481.pdf","host_type":"BRONZE"},{"url":"https://jme.bioscientifica.com/downloadpdf/journals/jme/32/2/481.pdf","host_type":"publisher"},{"url":"https://jme.bioscientifica.com/view/journals/jme/32/2/481.xml","host_type":"publisher"},{"url":"https://jme.bioscientifica.com/downloadpdf/journals/jme/32/2/481.xml","host_type":"publisher"},{"url":"https://doi.org/10.1677/jme.0.0320481","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15072553","host_type":"repository"}],"fields_of_study":["Estrogen and related hormone effects","Prostate Cancer Treatment and Research","RNA Research and Splicing","Biology","Medicine","Chemistry","Actinin","Amino Acid Motifs","Amino Acid Sequence","Animals","Binding Sites","Cells, Cultured","Conserved Sequence","Dimerization","Gene Expression Regulation, Developmental","HeLa Cells","Humans","Male","Mice","Microfilament Proteins","Molecular Sequence Data","Myoblasts","Nuclear Receptor Coactivator 2","Protein Structure, Tertiary","Receptors, Cytoplasmic and Nuclear","Transcription Factors","Transcriptional Activation"],"mesh_terms":["Actinin","Amino Acid Sequence","Animals","Binding Sites","Cells, Cultured","HeLa Cells","Humans","Male","Microfilament Proteins","Molecular Sequence Data","Transcription Factors","Transcriptional Activation","Conserved Sequence","Protein Structure, Tertiary","Receptors, Cytoplasmic and Nuclear","Gene Expression Regulation, Developmental","Dimerization","Amino Acid Motifs","Myoblasts","Mice","Nuclear Receptor Coactivator 2","Hela Cells"],"keywords":["Coactivator","Nuclear receptor coactivator 3","Nuclear receptor coactivator 1","Nuclear receptor coactivator 2","Nuclear receptor","Estrogen-related receptor alpha","Transactivation","Cell biology","Activator (genetics)","Nuclear receptor co-repressor 1","Estrogen-related receptor gamma","Biology","Thyroid hormone receptor","Chemistry","Transcription factor","Receptor","Molecular biology","Estrogen receptor","Biochemistry","Genetics"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T22:13:00.343354Z","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":[]}