AKT phosphorylates MDM2

Stable Identifier
Reaction [transition]
Homo sapiens
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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).
Literature References
PubMed ID Title Journal Year
15527798 A novel site of AKT-mediated phosphorylation in the human MDM2 onco-protein

Kampanis, P, Campbell, DG, Nicol, S, Milne, D, Meek, D, Fuller-Pace, F, Dias, S

FEBS Lett. 2004
15169778 Stabilization of Mdm2 via decreased ubiquitination is mediated by protein kinase B/Akt-dependent phosphorylation

Yang, Z, Hess, D, Tamaskovic, R, Merlo, A, Feng, J, Brazil, DP, Hemmings, BA

J. Biol. Chem. 2004
11504915 A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus

Mayo, LD, Donner, DB

Proc. Natl. Acad. Sci. U.S.A. 2001
11715018 HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation

Zou, Y, Xia, W, Zhou, BP, Hung, MC, Spohn, B, Liao, Y

Nat Cell Biol 2001
Event Information
Go Biological Process
Catalyst Activity

protein serine/threonine kinase activity of p-T,p-S-AKT [cytosol]

Orthologous Events
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