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National Academy of Sciences, Proceedings of the National Academy of Sciences, 4(118), 2021
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Mdm2 phosphorylation by Akt regulates the p53 response to oxidative stress to promote cell proliferation and tumorigenesis
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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.