Reactome | AKT phosphorylates MDM2

AKT phosphorylates MDM2

Stable Identifier

R-HSA-198599

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

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)

General

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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

Participants

Input

Output

Participant Of

hasEvent

Event Information

Go Biological Process

protein kinase B signaling (0043491)

Catalyst Activity

Title

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

Physical Entity

p-T,p-S-AKT [cytosol]

Activity

protein serine/threonine kinase activity (0004674)

Orthologous Events

AKT phosphorylates MDM2 (Caenorhabditis elegans)

AKT phosphorylates MDM2 (Canis familiaris)

AKT phosphorylates MDM2 (Drosophila melanogaster)

AKT phosphorylates MDM2 (Gallus gallus)

AKT phosphorylates MDM2 (Mus musculus)

AKT phosphorylates MDM2 (Rattus norvegicus)

AKT phosphorylates MDM2 (Schizosaccharomyces pombe)

AKT phosphorylates MDM2 (Sus scrofa)

AKT phosphorylates MDM2 (Xenopus tropicalis)

Authored

Nasi, S (2006-10-10)

Annibali, D (2006-10-10)

Reviewed

Greene, LA (2007-11-08)

Zaccara, S (2016-02-04)

Inga, A (2016-02-04)

Created

Jassal, B (2007-06-29)