{"doi":"10.1091/mbc.11.6.2007","title":"Interaction of the τ2 Transcriptional Activation Domain of Glucocorticoid Receptor with a Novel Steroid Receptor Coactivator, Hic-5, Which Localizes to Both Focal Adhesions and the Nuclear Matrix","abstract":"<jats:p>Hic-5 (hydrogen peroxide–inducible clone-5) is a focal adhesion protein that is involved in cellular senescence. In the present study, a yeast two-hybrid screen identified Hic-5 as a protein that interacts with a region of the glucocorticoid receptor that includes a nuclear matrix–targeting signal and the τ2 transcriptional activation domain. In transiently transfected mammalian cells, overexpression of Hic-5 potentiated the activation of reporter genes by all steroid receptors, excluding the estrogen receptor. The activity of the estrogen receptor and the thyroid hormone receptor was stimulated by Hic-5 in the presence but not in the absence of coexpressed coactivator GRIP1. In biochemical fractionations and indirect immunofluorescence assays, a fraction of endogenous Hic-5 in REF-52 cells and transiently expressed Hic-5 in Cos-1 cells was associated with the nuclear matrix. The C-terminal region of Hic-5, which contains seven zinc fingers arranged in four LIM domains, was required for interaction with focal adhesions, the nuclear matrix, steroid receptors, and the τ2 domain of glucocorticoid receptor. The N-terminal region of Hic-5 possesses a transcriptional activation domain and was essential for the coactivator activity of Hic-5. Given the coexisting cytoplasmic and nuclear distributions of Hic-5 and its role in steroid receptor–mediated transcriptional activation, it is proposed that Hic-5 might transmit signals that emanate at cell attachment sites and regulate transcription factors, such as steroid receptors.</jats:p>","journal":"Molecular Biology of the Cell","year":2000,"id":24908,"datarank":6.131458516086109,"base_score":4.890349128221754,"endowment":4.890349128221754,"self_citation_contribution":0.7335523692332632,"citation_network_contribution":5.397906146852846,"self_endowment_contribution":0.7335523692332632,"citer_contribution":5.397906146852846,"corpus_percentile":null,"corpus_rank":null,"citation_count":132,"citer_count":115,"citers_with_citation_signal":104,"citers_with_endowment":104,"datacite_reuse_total":1,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":148068,"name":"Jennifer Guerrero","orcid":null,"position":1,"is_corresponding":false},{"id":143087,"name":"Heng Hong","orcid":null,"position":2,"is_corresponding":false},{"id":148069,"name":"Donald B. DeFranco","orcid":null,"position":3,"is_corresponding":false},{"id":143092,"name":"Michael R. Stallcup","orcid":null,"position":4,"is_corresponding":false},{"id":148067,"name":"Lan Yang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.890349128221754,"endowment":4.890349128221754,"datacite_reuse_total":1,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10848625","pmcid":"PMC14899","openalex_id":"https://openalex.org/W2159762082","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"R01 CA043037","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK043093","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK43093","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA43037","title":null}],"total_grants":4,"fwci":7.8197,"citation_percentile":0.97631916,"influential_citations":11,"citation_trend":[{"year":2012,"count":2},{"year":2014,"count":3},{"year":2015,"count":3},{"year":2016,"count":5},{"year":2017,"count":7},{"year":2018,"count":3},{"year":2019,"count":1},{"year":2020,"count":2},{"year":2021,"count":3},{"year":2022,"count":3},{"year":2024,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://europepmc.org/articles/pmc14899?pdf=render","host_type":"GREEN"},{"url":"https://doi.org/10.1091/mbc.11.6.2007","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10848625","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/14899","host_type":"repository"}],"fields_of_study":["Estrogen and related hormone effects","Cancer-related gene regulation","RNA Research and Splicing","Biology","Medicine","Chemistry","Animals","Binding Sites","COS Cells","Cell Line","Cell Nucleus","Chlorocebus aethiops","Cytoplasm","Cytoskeletal Proteins","DNA-Binding Proteins","Humans","Intracellular Signaling Peptides and Proteins","LIM Domain Proteins","Mice","Nuclear Matrix","Receptors, Androgen","Receptors, Glucocorticoid","Receptors, Mineralocorticoid","Receptors, Progesterone","Transcriptional Activation","Zinc Fingers"],"mesh_terms":["Animals","Binding Sites","Cell Line","Cell Nucleus","Chlorocebus aethiops","Cytoplasm","Cytoskeletal Proteins","DNA-Binding Proteins","Humans","Receptors, Androgen","Receptors, Glucocorticoid","Receptors, Progesterone","Nuclear Matrix","Transcriptional Activation","Zinc Fingers","Receptors, Mineralocorticoid","COS Cells","Intracellular Signaling Peptides and Proteins","Mice","LIM Domain Proteins"],"keywords":["Nuclear receptor coactivator 2","Nuclear receptor coactivator 1","Coactivator","Nuclear receptor coactivator 3","Nuclear receptor","Biology","Glucocorticoid receptor","Cell biology","PELP-1","Nuclear receptor co-repressor 1","Focal adhesion","Estrogen-related receptor gamma","Receptor","Estrogen receptor","Hormone response element","Estrogen-related receptor alpha","Nuclear matrix","Signal transduction","Transcription factor","Biochemistry","Chromatin","Genetics","Gene"],"sdg_mappings":[],"linked_datasets":[{"doi":"10.17920/g9x10x","title":"NCCC Breast Cancer Research Training Program","publisher":"University of California Office of the President","resource_type":"Award"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T23:30:43.196995Z","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,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}