Cdc25B is transcriptionally inhibited by IER5 through the NF-YB transcription factor in irradiation-treated HeLa cells
| Autor: | Xiaoyan Jiang, Xianzhe Zhao, Kuke Ding, Ping-Kun Zhou, Qiang Xiong, Xiao-Dan Liu, Lixin Ding |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Paper
0301 basic medicine biology Chemistry Health Toxicology and Mutagenesis Promoter Cell cycle Toxicology biology.organism_classification Molecular biology HeLa 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Downregulation and upregulation 030220 oncology & carcinogenesis Coactivator Transcriptional regulation Transcription factor Chromatin immunoprecipitation |
| Zdroj: | Toxicol Res (Camb) |
| ISSN: | 2045-4538 |
| DOI: | 10.1093/toxres/tfab069 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|