Mdm2 phosphorylation by Akt regulates the p53 response to oxidative stress to promote cell proliferation and tumorigenesis
Loretah Chibaya, Baktiar Karim, Hong Zhang, Stephen N. Jones
Abstract
Significance We demonstrate that Akt phosphorylation of Mdm2 protein at Ser183 inhibits p53-mediated senescence and promotes ROS-induced tumorigenesis. Thus, different effector kinases can modify Mdm2 and selectively regulate the p53-mediated response to stress. Our study suggests that targeted inhibition of Mdm2 Ser183 phosphorylation would activate p53-mediated senescence and delay tumor progression.
Topics & Concepts
Protein kinase BMdm2PhosphorylationCarcinogenesisDNA damageOxidative stressCancer researchCell biologySignal transductionBiologyChemistryCancerApoptosisBiochemistryDNAGeneticsCancer-related Molecular PathwaysCancer, Hypoxia, and MetabolismRetinoids in leukemia and cellular processes