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Increased Sensitivity to UV Radiation in Mice with a p53 Point Mutation at Ser389

Year: 2004
Type: article
Abstract: 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.
DOI: 10.1128/mcb.24.20.8884-8894.2004
Authors: Wendy Bruins, Edwin Zwart, Laura D. Attardi, Tomoo Iwakuma, Esther M. Hoogervorst, Rudolf B. Beems, Barbara Miranda, Conny T. M. van Oostrom, Jolanda van den Berg, Gerard J. van den Aardweg, Guillermina Lozano, Harry van Steeg, Tyler Jacks, Annemieke de Vries
Institutions: National Institute for Public Health and the Environment, Stanford Medicine, Stanford University, The University of Texas MD Anderson Cancer Center, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Erasmus University Rotterdam
Language: English
Subfield: Oncology
Field: Medicine
Open Access status: green
OpenAlex ID: W2158155127
FWCI: 4.992
Cites: 45
Cited by: 121
Related to: 10