AKT phosphorylates MDM2 on two serine residues, at positions 166 and 188 (Mayo and Donner 2001, Feng et al. 2004, Milne et al. 2004). AKT-mediated phosphorylation of the E3 ubiquitin-protein ligase MDM2 promotes nuclear localization and interferes with the interaction between MDM2 and p14-ARF, thereby decreasing p53 stability. This leads to a decreased expression of p53 target genes, such as BAX, that promote apoptosis (Zhou et al. 2001, Mayo and Donner 2001).
Kampanis, P, Campbell, DG, Nicol, S, Milne, D, Meek, D, Fuller-Pace, F, Dias, S
Yang, Z, Hess, D, Tamaskovic, R, Merlo, A, Feng, J, Brazil, DP, Hemmings, BA
Mayo, LD, Donner, DB
Zou, Y, Xia, W, Zhou, BP, Hung, MC, Spohn, B, Liao, Y
protein serine/threonine kinase activity of p-T,p-S-AKT [cytosol]
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