BRCA2 represses the transcriptional activity of pS2 by E2-ERα
| Autor: | Mio Fukuda, Yo Tojo, Ami Sato, Hiroko Saito, Akira Nakanishi, Yoshio Miki |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
BRCA2 Protein
Estradiol Transcription Genetic Estrogen Receptor alpha Biophysics Proteins Cell Biology Biochemistry Gene Expression Regulation Neoplastic Nuclear Receptor Coactivator 1 Protein Domains MCF-7 Cells Humans Trefoil Factor-1 Promoter Regions Genetic Molecular Biology Protein Binding Transcription Factors |
| Zdroj: | Biochemical and Biophysical Research Communications. 588:75-82 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2021.12.054 |
| Popis: | Germline mutations to the breast cancer 2 (BRCA2) gene have been associated with hereditary breast cancer. In addition to estrogen uptake, BRCA2 expression increases in the S phase of the cell cycle and largely contributes to DNA damage repair associated with DNA replication. However, the role of BRCA2 in estrogen induction remains unclear. An expression plasmid was created to induce BRCA2 activation upon the addition of estradiol by introducing mutations to the binding sequences for the transcription factors USF1, E2F1, and NF-κB within the promoter region of BRCA2. Then, the estrogen receptor (ER) sites of the proteins that interact with BRCA2 upon the addition of estradiol were identified. Both proteins were bound by the helical domain of BRCA2 and activation function-2 of the ER, suggesting that this binding may regulate the transcriptional activity of pS2, a target gene of the estradiol-ER, by suppressing the binding of SRC-1, a coactivator required for activation of the transcription factor. |
| Databáze: | OpenAIRE |
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