Title: The p53 mRNA-Mdm2 interaction controls Mdm2 nuclear trafficking and is required for p53 activation following DNA damage
Authors: Gajjar, Madhavsai ×
Candeias, Marco M
Malbert-Colas, Laurence
Mazars, Anne
Fujita, Jun
Olivares-Illana, Vanesa
Fåhraeus, Robin #
Issue Date: Jan-2012
Publisher: Cell Press
Series Title: Cancer Cell vol:21 issue:1 pages:25-35
Article number: 10.1016/j.ccr.2011.11.016
Abstract: The ATM kinase and p53 are key tumor suppressor factors that control the genotoxic stress response pathway. The ATM substrate Mdm2 controls p53 activity by either targeting p53 for degradation or promoting its synthesis by binding the p53 mRNA. The physiological role and regulation of Mdm2's dual function toward p53 is not known. Here we show that ATM-dependent phosphorylation of Mdm2 at Ser395 is required for the p53 mRNA-Mdm2 interaction. This event also promotes SUMO-conjugation of Mdm2 and its nucleoli accumulation. Interfering with the p53 mRNA-Mdm2 interaction prevents p53 stabilization and activation following DNA damage. These results demonstrate how ATM activity switches Mdm2 from a negative to a positive regulator of p53 via the p53 mRNA.
ISSN: 1535-6108
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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