{"doi":"10.1083/jcb.144.4.645","title":"A Monoclonal Antibody to the COOH-terminal Acidic Portion of Ran Inhibits Both the Recycling of Ran and Nuclear Protein Import in Living Cells","abstract":"<jats:p>A small GTPase Ran is a key regulator for active nuclear transport. In immunoblotting analysis, a monoclonal antibody against recombinant human Ran, designated ARAN1, was found to recognize an epitope in the COOH-terminal domain of Ran. In a solution binding assay, ARAN1 recognized Ran when complexed with importin β, transportin, and CAS, but not the Ran-GTP or the Ran-GDP alone, indicating that the COOH-terminal domain of Ran is exposed via its interaction with importin β–related proteins. In addition, ARAN1 suppressed the binding of RanBP1 to the Ran–importin β complex. When injected into the nucleus of BHK cells, ARAN1 was rapidly exported to the cytoplasm, indicating that the Ran–importin β–related protein complex is exported as a complex from the nucleus to the cytoplasm in living cells. Moreover, ARAN1, when injected into the cultured cells induces the accumulation of endogenous Ran in the cytoplasm and prevents the nuclear import of SV-40 T-antigen nuclear localization signal substrates. From these findings, we propose that the binding of RanBP1 to the Ran–importin β complex is required for the dissociation of the complex in the cytoplasm and that the released Ran is recycled to the nucleus, which is essential for the nuclear protein transport.</jats:p>","journal":"The Journal of Cell Biology","year":1999,"id":616475,"datarank":0.6261580904843456,"base_score":4.174387269895637,"endowment":4.174387269895637,"self_citation_contribution":0.6261580904843456,"citation_network_contribution":0.0,"self_endowment_contribution":0.6261580904843456,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":64,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1589431,"name":"Taro Tachibana","orcid":null,"position":1,"is_corresponding":false},{"id":1589432,"name":"Fumihiko Yokoya","orcid":null,"position":2,"is_corresponding":false},{"id":1589433,"name":"Shingo Kose","orcid":null,"position":3,"is_corresponding":false},{"id":1589434,"name":"Naoko Imamoto","orcid":null,"position":4,"is_corresponding":false},{"id":1589435,"name":"Yoshihiro Yoneda","orcid":null,"position":5,"is_corresponding":false},{"id":1589430,"name":"Miki Hieda","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A Monoclonal Antibody to the COOH-terminal Acidic Portion of Ran Inhibits Both the Recycling of Ran and Nuclear Protein Import in Living Cells","abstract":"<jats:p>A small GTPase Ran is a key regulator for active nuclear transport. In immunoblotting analysis, a monoclonal antibody against recombinant human Ran, designated ARAN1, was found to recognize an epitope in the COOH-terminal domain of Ran. In a solution binding assay, ARAN1 recognized Ran when complexed with importin β, transportin, and CAS, but not the Ran-GTP or the Ran-GDP alone, indicating that the COOH-terminal domain of Ran is exposed via its interaction with importin β–related proteins. In addition, ARAN1 suppressed the binding of RanBP1 to the Ran–importin β complex. When injected into the nucleus of BHK cells, ARAN1 was rapidly exported to the cytoplasm, indicating that the Ran–importin β–related protein complex is exported as a complex from the nucleus to the cytoplasm in living cells. Moreover, ARAN1, when injected into the cultured cells induces the accumulation of endogenous Ran in the cytoplasm and prevents the nuclear import of SV-40 T-antigen nuclear localization signal substrates. From these findings, we propose that the binding of RanBP1 to the Ran–importin β complex is required for the dissociation of the complex in the cytoplasm and that the released Ran is recycled to the nucleus, which is essential for the nuclear protein transport.</jats:p>","is_dataset_classified":null,"base_score":4.174387269895637,"endowment":4.174387269895637,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10037787","pmcid":"PMC2132938","openalex_id":"https://openalex.org/W2076208916","authors":[],"funders":[{"funder_name":"NCIPC CDC HHS","grant_id":"U17 CE002006","title":null}],"total_grants":1,"fwci":4.0845,"citation_percentile":0.94657898,"influential_citations":0,"citation_trend":[{"year":2013,"count":3},{"year":2014,"count":1},{"year":2018,"count":1},{"year":2021,"count":5},{"year":2023,"count":2}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://rupress.org/jcb/article-pdf/144/4/645/1283719/9807158.pdf","host_type":"journal"},{"url":"https://rupress.org/jcb/article-pdf/144/4/645/1283719/9807158.pdf","host_type":"publisher"},{"url":"https://rupress.org/jcb/article-pdf/144/4/645/1848208/9807158.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1083/jcb.144.4.645","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10037787","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.274.1585","host_type":""},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2132938","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC2132938","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC2132938?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Nuclear Structure and Function","RNA Research and Splicing","DNA Repair Mechanisms","Amino Acid Sequence","Animals","Antibodies, Monoclonal","Base Sequence","Biological Transport, Active","Cell Line","Cell Nucleus","Cricetinae","Cytoplasm","DNA Primers","Epitopes","GTP Phosphohydrolases","GTP-Binding Proteins","Humans","Karyopherins","Macromolecular Substances","Mice","Nuclear Proteins","Recombinant Proteins","ran GTP-Binding Protein"],"mesh_terms":["Amino Acid Sequence","Animals","Antibodies, Monoclonal","Epitopes","Base Sequence","Biological Transport, Active","Cell Line","Cell Nucleus","Cytoplasm","Cricetinae","Humans","Nuclear Proteins","Recombinant Proteins","DNA Primers","GTP-Binding Proteins","GTP Phosphohydrolases","ran GTP-Binding Protein","Karyopherins","Macromolecular Substances","Mice"],"keywords":["Ran","Importin","Nuclear transport","Cytoplasm","Biology","Nuclear localization sequence","Nuclear protein","Cell biology","Nuclear pore","Cell nucleus","Molecular biology","Biochemistry","Transcription factor","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Decent work and economic growth"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T22:59:46.669398Z","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":[]}