Reactome | AKT phosphorylates MDM2

AKT phosphorylates MDM2

Stable Identifier

R-HSA-198599

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

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Gene expression (Transcription) (Homo sapiens)

- RNA Polymerase II Transcription (Homo sapiens)
  - Generic Transcription Pathway (Homo sapiens)
    - Transcriptional Regulation by TP53 (Homo sapiens)
      - Regulation of TP53 Activity (Homo sapiens)
        
        Regulation of TP53 Expression and Degradation (Homo sapiens)
        
        Regulation of TP53 Degradation (Homo sapiens)
        
        AKT phosphorylates MDM2 (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 Milne, D, Kampanis, P, Nicol, S, Dias, S, Campbell, DG, Fuller-Pace, F, Meek, D	FEBS Lett.	2004
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
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