A transactivation-deficient mouse model provides insights into Trp53 regulation and function
| العنوان: | A transactivation-deficient mouse model provides insights into Trp53 regulation and function |
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| المؤلفون: | Erin A. Barcarse, Jayne M. Stommel, Geoffrey M. Wahl, Michelle Beeche, Xiao Qun Zhang, Monica Nistér, Stephen O'Gorman, Gretchen S. Jimenez |
| المصدر: | Nature Genetics. 26:37-43 |
| بيانات النشر: | Springer Science and Business Media LLC, 2000. |
| سنة النشر: | 2000 |
| مصطلحات موضوعية: | Transcriptional Activation, Tumor suppressor gene, DNA damage, animal diseases, Mutant, Apoptosis, Mice, Transgenic, medicine.disease_cause, Mice, Transactivation, Tumor Suppressor Protein p14ARF, Genetics, medicine, Animals, Gene, Alleles, Nucleic Acid Synthesis Inhibitors, Mutation, biology, Genes, p53, Cell biology, Gene Expression Regulation, Neoplastic, Models, Animal, Dactinomycin, biology.protein, Mdm2, Female, Tumor Suppressor Protein p53, Carcinogenesis, Neoplasm Transplantation, DNA Damage |
| الوصف: | The gene Trp53 is among the most frequently mutated and studied genes in human cancer, but the mechanisms by which it suppresses tumour formation remain unclear. We generated mice with an allele encoding changes at Leu25 and Trp26, known to be essential for transcriptional transactivation and Mdm2 binding, to enable analyses of Trp53 structure and function in vivo. The mutant Trp53 was abundant, its level was not affected by DNA damage and it bound DNA constitutively; however, it showed defects in cell-cycle regulation and apoptosis. Both mutant and Trp53-null mouse embryonic fibroblasts (MEFs) were readily transformed by oncogenes, and the corresponding mice were prone to tumours. We conclude that the determining pathway for Trp53 tumour-suppressor function in mice requires the transactivation domain. |
| تدمد: | 1546-1718 1061-4036 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::182f944daf39f13f4860fadd6374c7aa https://doi.org/10.1038/79152 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....182f944daf39f13f4860fadd6374c7aa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15461718 10614036 |
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