{"doi":"10.1093/toxres/tfab069","title":"<i>Cdc25B</i> is transcriptionally inhibited by <i>IER5</i> through the <i>NF-YB</i> transcription factor in irradiation-treated HeLa cells","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Cervical cancer (CC) is a type of pelvic malignant tumor that severely threatens women's health. Current evidence suggests that IER5, as a potential radiosensitizer, promotes irradiation-induced apoptosis in CC tissues in patients undergoing chemoradiotherapy. IER5 has been shown to be involved in the G2/M-phase transition. In the present study, we used Cdc25B as the breakthrough point to explore the underlying mechanism of IER5 in the cell cycle regulation of radiation-damaged HeLa cells. IER5 was evidently upregulated after irradiation, but Cdc25B was significantly downregulated. In monoclonal IER5-silenced HeLa cells, irradiation-induced downregulation of Cdc25B was attenuated. The effect of irradiation on Cdc25B promoter activity was determined by dual-luciferase reporter assays. The response elements on the Cdc25B promoter related to irradiation were predicted by JASPAR. These conserved sequences were mutated individually or in combination by splicing-by-overlap extension PCR, and their function was confirmed by dual-luciferase reporter assays. The enrichment efficiency of transcription factors after irradiation was determined by chromatin immunoprecipitation (ChIP) assay. Both Sp1/Sp3 and NF-YB binding sites were involved in irradiation-mediated regulation of Cdc25B. IER5 was involved in irradiation-mediated regulation of Cdc25B through the NF-YB binding site. Furthermore, ChIP assays showed that IER5 bound to the Cdc25B promoter, and the binding of IER5 to the Cdc25B promoter region in irradiation-induced HeLa cells induced the release of the coactivator p300 through interaction with NF-YB. Taken together, these findings indicate that IER5 is the transcriptional repressor that accelerates the downregulation of Cdc25B expression after irradiation.</jats:p>","journal":"Toxicology Research","year":2021,"id":634864,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"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":1646795,"name":"Xianzhe Zhao","orcid":null,"position":1,"is_corresponding":false},{"id":927865,"name":"Qiang Xiong","orcid":"0000-0002-3022-3956","position":2,"is_corresponding":false},{"id":880405,"name":"Xiaoyan Jiang","orcid":"0000-0002-8974-7340","position":3,"is_corresponding":false},{"id":1297094,"name":"Xiaodan Liu","orcid":"0000-0003-1500-9086","position":4,"is_corresponding":false},{"id":1646798,"name":"Kuke Ding","orcid":null,"position":5,"is_corresponding":false},{"id":171433,"name":"Pingkun Zhou","orcid":null,"position":6,"is_corresponding":false},{"id":1646794,"name":"Lixin Ding","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"<i>Cdc25B</i> is transcriptionally inhibited by <i>IER5</i> through the <i>NF-YB</i> transcription factor in irradiation-treated HeLa cells","abstract":"Abstract Cervical cancer (CC) is a type of pelvic malignant tumor that severely threatens women's health. Current evidence suggests that IER5, as a potential radiosensitizer, promotes irradiation-induced apoptosis in CC tissues in patients undergoing chemoradiotherapy. IER5 has been shown to be involved in the G2/M-phase transition. In the present study, we used Cdc25B as the breakthrough point to explore the underlying mechanism of IER5 in the cell cycle regulation of radiation-damaged HeLa cells. IER5 was evidently upregulated after irradiation, but Cdc25B was significantly downregulated. In monoclonal IER5-silenced HeLa cells, irradiation-induced downregulation of Cdc25B was attenuated. The effect of irradiation on Cdc25B promoter activity was determined by dual-luciferase reporter assays. The response elements on the Cdc25B promoter related to irradiation were predicted by JASPAR. These conserved sequences were mutated individually or in combination by splicing-by-overlap extension PCR, and their function was confirmed by dual-luciferase reporter assays. The enrichment efficiency of transcription factors after irradiation was determined by chromatin immunoprecipitation (ChIP) assay. Both Sp1/Sp3 and NF-YB binding sites were involved in irradiation-mediated regulation of Cdc25B. IER5 was involved in irradiation-mediated regulation of Cdc25B through the NF-YB binding site. Furthermore, ChIP assays showed that IER5 bound to the Cdc25B promoter, and the binding of IER5 to the Cdc25B promoter region in irradiation-induced HeLa cells induced the release of the coactivator p300 through interaction with NF-YB. Taken together, these findings indicate that IER5 is the transcriptional repressor that accelerates the downregulation of Cdc25B expression after irradiation.","is_dataset_classified":null,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34484679","pmcid":"PMC8403591","openalex_id":"https://openalex.org/W3191053904","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"31640022","title":null},{"funder_name":"Natural Science Foundation of Beijing Municipality","grant_id":"7172146","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"31770907","title":null}],"total_grants":3,"fwci":0.3939,"citation_percentile":0.4948436,"influential_citations":0,"citation_trend":[{"year":2022,"count":1},{"year":2023,"count":2},{"year":2024,"count":2},{"year":2025,"count":1}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://academic.oup.com/toxres/article-pdf/10/4/875/40081066/tfab069.pdf","host_type":"journal"},{"url":"https://academic.oup.com/toxres/article-pdf/10/4/875/40081066/tfab069.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/toxres/tfab069","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34484679","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8403591","host_type":"repository"}],"fields_of_study":["Cancer-related molecular mechanisms research","Viral-associated cancers and disorders","NF-κB Signaling Pathways"],"mesh_terms":[],"keywords":["HeLa","Transcription factor","Transcription (linguistics)","Irradiation","Cancer research","Chemistry","Cell biology","Molecular biology","Biology","Physics","Biochemistry","Gene","In vitro","Transcription regulation","Cervical cancer","Cdc25b","Nf-yb","Ier5"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"hpa"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T14:17:11.880691Z","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":[]}