Increased Sensitivity to UV Radiation in Mice with a p53 Point Mutation at Ser389
| Autor: | Laura D. Attardi, Harry van Steeg, Edwin P. Zwart, Tomoo Iwakuma, Wendy Bruins, Rudolf B. Beems, Guillermina Lozano, Barbara Miranda, Conny T. M. van Oostrom, Jolanda van den Berg, Tyler Jacks, Gerard J. van den Aardweg, Annemieke de Vries, Esther M. Hoogervorst |
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| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Transcriptional Activation
DNA damage Ultraviolet Rays Mutant Apoptosis Thymus Gland Biology Serine Mice In vivo Animals Humans Point Mutation Neoplasms Squamous Cell Phosphorylation Molecular Biology Cell Growth and Development Cells Cultured Skin Antibiotics Antineoplastic Papilloma Point mutation Stem Cells Carcinoma Cell Cycle Cell Biology Cell cycle Fibroblasts Molecular biology Survival Rate Phenotype Gene Expression Regulation Doxorubicin Gamma Rays Tumor Suppressor Protein p53 |
| Popis: | Phosphorylation is important for p53 protein stabilization and activation after DNA damage. Serine 389 of p53 is specifically phosphorylated after UV irradiation, whereas gamma radiation activates p53 through a different pathway. To study the in vivo significance of p53 phosphorylation at serine 389, we generated a physiological mouse model in which p53 phosphorylation at serine 389 is abolished by alanine substitution. Homozygous mutant p53.S389A mice are viable and have an apparently normal phenotype. However, cells isolated from these mice are partly compromised in transcriptional activation of p53 target genes and apoptosis after UV irradiation, whereas gamma radiation-induced responses are not affected. Moreover, p53.S389A mice show increased sensitivity to UV-induced skin tumor development, signifying the importance of serine 389 phosphorylation for the tumor-suppressive function of p53. |
| Databáze: | OpenAIRE |
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