Jan 21, 2021 · Akt phosphorylation of Mdm2 serine residue 183 increases nuclear Mdm2 stability, decreases p53 levels, and prevents senescence in primary cells exposed to reactive oxidative species (ROS).

Jan 19, 2021 · 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.

Dec 14, 2012 · Here we report a novel Akt signaling pathway elicited by MDM2. Upregulation of endogenous MDM2 promotes, whereas its downregulation diminishes, Akt phosphorylation irrespective of p53...

Here we report a novel Akt signaling pathway elicited by MDM2. Upregulation of endogenous MDM2 promotes, whereas its downregulation diminishes, Akt phosphorylation irrespective of p53 status.

Jun 14, 2002 · Mdm2, a ubiquitin ligase for p53, plays a central role in regulation of the stability of p53 and serves as a good substrate for Akt. In this study, we find that expression of Akt reduces the protein levels of p53, at least in part by enhancing the degradation of p53.

The current paradigm states that the Akt signaling pathway phosphorylates the human oncoprotein mouse double minute 2 (MDM2), leading to its nuclear translocation and degradation of the tumor suppressor p53. Here we report a novel Akt signaling pathway elicited by MDM2.

Using multiple mouse models of ROS-induced cancer, we show that Mdm2 phosphorylation by Akt reduces senescence to pro-mote KrasG12D-driven lung cancers and carcinogen-induced papil-loma and hepatocellular carcinomas.

As both AKT signaling and decreased ERα levels are linked to tamoxifen resistance, our data suggest that combining MDM2 and AKT inhibitors may be more efficient to trigger tumor regression and/or limit the risk of resistance acquisition to anti-estrogenic drugs.

Mdm2, a ubiquitin ligase for p53, plays a central role in regulation of the stability of p53 and serves as a good substrate for Akt. In this study, we find that expression of Akt reduces the protein levels of p53, at least in part by enhancing the degradation of p53.

Feb 20, 2002 · Taken together, our findings suggest that depending on the balance of signals, p53-dependent downregulation of Akt may promote an irreversible commitment to apoptotic cell death, whereas...