Cell type- and promoter-specific roles of Ser18 phosphorylation in regulating p53 responses.
Détails
ID Serval
serval:BIB_28415
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Cell type- and promoter-specific roles of Ser18 phosphorylation in regulating p53 responses.
Périodique
Journal of Biological Chemistry
ISSN
0021-9258
Statut éditorial
Publié
Date de publication
2003
Volume
278
Numéro
42
Pages
41028-41033
Langue
anglais
Résumé
Phosphorylation of mouse p53 at Ser18 occurs after DNA damage. To determine the physiological roles of this phosphorylation event in p53-dependent DNA damage responses, a Ser18 to Ala missense mutation was introduced into the germline of mice. Thymocytes and fibroblasts from the knock-in mice show reduced transactivation of many p53 target genes following DNA damage. p53 protein stabilization and DNA binding are similar in knock-in and wild type mice, but C-terminal acetylation was defective, consistent with a role for Ser18 in the recruitment of transcriptional co-activators. The apoptotic response of knock-in thymocytes to ionizing radiation is intermediate between that of wild type and p53 null thymocytes. Despite impaired transcriptional and apoptotic responses, the knock-in mice are not prone to spontaneous tumorigenesis. This indicates that neither phosphorylation of p53 on Ser18 by ATM nor a full transcriptional response is essential to prevent spontaneous tumor formation in mice.
Mots-clé
Animals, Apoptosis, Blotting, Western, Cell Cycle, Cell Cycle Proteins, Chromatin/metabolism, DNA Damage, DNA-Binding Proteins, Dose-Response Relationship, Radiation, Fibroblasts/metabolism, Mice, Mice, Transgenic, Oligonucleotide Array Sequence Analysis, Phosphorylation, Precipitin Tests, Promoter Regions, Genetic, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases/metabolism, RNA, Messenger/metabolism, Reverse Transcriptase Polymerase Chain Reaction, Serine/chemistry, Serine/metabolism, Thymus Gland/cytology, Thymus Gland/metabolism, Time Factors, Transcription, Genetic, Transcriptional Activation, Tumor Suppressor Protein p53/metabolism, Tumor Suppressor Proteins, Ultraviolet Rays
OAI-PMH
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/11/2007 12:25
Dernière modification de la notice
20/08/2019 13:07