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
Auteur⸱e⸱s
Chao C., Hergenhahn M., Kaeser M.D., Wu Z., Saito S., Iggo R., Hollstein M., Appella E., Xu Y.
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
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
Données d'usage