Cross-regulation between Egr-1 and APE/Ref-1 during early response to oxidative stress in the human osteoblastic HOBIT cell line: Evidence for an autoregulatory loop
| العنوان: | Cross-regulation between Egr-1 and APE/Ref-1 during early response to oxidative stress in the human osteoblastic HOBIT cell line: Evidence for an autoregulatory loop |
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| المؤلفون: | Alex Pines, Gianluca Tell, Mark R. Kelley, Milena Romanello, Eileen D. Adamson, Luigi Moro, Nicoletta Bivi, Franco Quadrifoglio, Paola D'Andrea, Giuseppe Damante |
| المساهمون: | Pines, A, Bivi, N, Romanello, M, Damante, G, Kelley, Mr, Adamson, Ed, D'Andrea, Paola, Quadrifoglio, F, Moro, L, Tell, G. |
| المصدر: | Free Radical Research. 39:269-281 |
| بيانات النشر: | Informa UK Limited, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Egr-1, DNA Repair, Transcription, Genetic, Electrophoretic Mobility Shift Assay, Biochemistry, APE/REF1, PKC, transcriptional regulation, redox regulation, DNA-(Apurinic or Apyrimidinic Site) Lyase, Transcriptional regulation, Promoter Regions, Genetic, Regulation of gene expression, DNA-repair, Zinc Fingers, General Medicine, Transfection, Oxidants, DNA-Binding Proteins, APE/Ref-1, Oxidation-Reduction, Chromatin Immunoprecipitation, Molecular Sequence Data, Biology, Thymidine Kinase, Immediate early protein, Cell Line, Immediate-Early Proteins, Humans, Transcription factor, Cell Proliferation, Early Growth Response Protein 1, Binding Sites, Osteoblasts, Base Sequence, Cell growth, Tumor Suppressor Proteins, PTEN Phosphohydrolase, Promoter, Redox regulation, DNA, Hydrogen Peroxide, Molecular biology, Phosphoric Monoester Hydrolases, body regions, Oxidative Stress, Gene Expression Regulation, Chromatin immunoprecipitation, Transcription Factors |
| الوصف: | The Early Growth Response protein (Egr-1) is a C(2)H(2)-zinc finger-containing transcriptional regulator involved in the control of cell proliferation and apoptosis. Its DNA-binding activity is redox regulated in vitro through the oxidation-reduction of Cys residues within its DNA-binding domain. APE/Ref-1 is a DNA-repair enzyme with redox modulating activities on several transcription factors. In this study, by evaluating the effects of different stimuli, we found a similar timing of activation being suggestive for a common and co-linear regulation for the two proteins. Indeed, we show that APE/Ref-1 increases the Egr-1 DNA-binding activity in unstimulated osteoblastic HOBIT cells. H(2)O(2) stimulation induces a strong interaction between Egr-1 and APE/Ref-1 at early times upon activation, as assayed by immunoprecipitation experiments. By using a cell transfection approach, we demonstrated the functional role of this interaction showing that two specific Egr-1 target genes, the PTEN phosphatase and the thymidine kinase (TK) genes promoters, are activated by contransfection of APE/Ref-1. Interestingly, by using a cell transfection approach and Chromatin immunoprecipitation assays, we were able to demonstrate that Egr-1 stimulates the transcriptional activity of APE/Ref-1 gene promoter by a direct interaction with specific DNA-binding site on its promoter. Taken together, our data delineate a new molecular mechanism of Egr-1 activation occurring soon after H(2)O(2) stimulation in osteoblastic cells and suggest a model for a positive loop between APE/Ref-1 and Egr-1 that could explain the early transcriptional activation of APE/Ref-1 gene expression. |
| وصف الملف: | STAMPA |
| تدمد: | 1029-2470 1071-5762 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::943016cc710f5542e6d03886a868539dTest https://doi.org/10.1080/10715760400028423Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....943016cc710f5542e6d03886a868539d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10292470 10715762 |
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