C/EBPα expression is partially regulated by C/EBPβ in response to DNA damage and C/EBPα-deficient fibroblasts display an impaired G1 checkpoint
| العنوان: | C/EBPα expression is partially regulated by C/EBPβ in response to DNA damage and C/EBPα-deficient fibroblasts display an impaired G1 checkpoint |
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| المؤلفون: | Robert C. Smart, Elizabeth A. Thompson, Rakesh Ranjan, Kyungsil Yoon |
| المصدر: | Oncogene |
| بيانات النشر: | Springer Science and Business Media LLC, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Male, Methylnitronitrosoguanidine, Cancer Research, Time Factors, Cell cycle checkpoint, Ultraviolet Rays, DNA damage, Blotting, Western, Gene Expression, Mice, Inbred Strains, Biology, digestive system, Article, S Phase, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, CCAAT-Enhancer-Binding Protein-alpha, Genetics, medicine, Animals, Electrophoretic mobility shift assay, Fibroblast, Molecular Biology, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, CCAAT-Enhancer-Binding Protein-beta, digestive, oral, and skin physiology, G1 Phase, G1/S transition, Fibroblasts, Cell cycle, Flow Cytometry, Molecular biology, 3. Good health, Mice, Inbred C57BL, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, Female, biological phenomena, cell phenomena, and immunity, Chromatin immunoprecipitation, hormones, hormone substitutes, and hormone antagonists, DNA, DNA Damage |
| الوصف: | We observed that CCAAT/enhancer-binding protein (C/EBP)alpha is highly inducible in primary fibroblasts by DNA-damaging agents that induce strand breaks, alkylate and crosslink DNA as well as those that produce bulky DNA lesions. Fibroblasts deficient in C/EBPalpha (C/EBPalpha(-/-)) display an impaired G1 checkpoint as evidenced by an inappropriate entry into the S-phase in response to DNA damage, and these cells also display an enhanced G1/S transition in response to mitogens. The induction of C/EBPalpha by DNA damage in fibroblasts does not require p53. Electrophoretic mobility shift assay (EMSA) analysis of nuclear extracts prepared from ultraviolet B (UVB)- and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated fibroblasts showed increased binding of C/EBPbeta to a C/EBP consensus sequence and chromatin immunoprecipitation (ChIP) analysis also showed increased C/EBPbeta binding to the C/EBPalpha promoter. To determine whether C/EBPbeta has a function in the regulation of C/EBPalpha, we treated C/EBPbeta(-/-) fibroblasts with UVB or MNNG. We observed that C/EBPalpha induction was impaired in both UVB- and MNNG-treated C/EBPbeta(-/-) fibroblasts. Our study shows a novel function for C/EBPbeta in the regulation of C/EBPalpha in response to DNA damage and provides definitive genetic evidence that C/EBPalpha has a critical role in the DNA damage G1 checkpoint. |
| تدمد: | 1476-5594 0950-9232 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cec7eaf96657945e914da6604fc35508Test https://doi.org/10.1038/onc.2009.176Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....cec7eaf96657945e914da6604fc35508 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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