AKT phosphorylates MDM2

Stable Identifier
R-HSA-198599
Type
Reaction [transition]
Species
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
15169778 Stabilization of Mdm2 via decreased ubiquitination is mediated by protein kinase B/Akt-dependent phosphorylation

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

J. Biol. Chem. 2004
15527798 A novel site of AKT-mediated phosphorylation in the human MDM2 onco-protein

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

FEBS Lett. 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

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

Nat Cell Biol 2001
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Title
protein serine/threonine kinase activity of p-T,p-S-AKT [cytosol]
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