◀ Back to AKT1
AKT1 — MDM2
Pathways - manually collected, often from reviews:
-
KEGG Pathways in cancer:
AKT1/AKT2/AKT3
→
MDM2
(protein-protein, activation)
-
KEGG Prostate cancer:
AKT1/AKT2/AKT3
→
MDM2
(protein-protein, activation)
-
KEGG Chronic myeloid leukemia:
AKT1/AKT2/AKT3
→
MDM2
(protein-protein, activation)
-
NCI Pathway Database p53 pathway:
AKT1 (AKT1)
→
MDM2/UBCH5 complex (MDM2-UBE2D1)
(modification, activates)
Mayo et al., Proc Natl Acad Sci U S A 2001, Zhou et al., Nat Cell Biol 2001
Evidence: mutant phenotype, assay, physical interaction
-
Reactome Reaction:
AKT1
→
MDM2
(reaction)
Zhou et al., Nat Cell Biol 2001, Feng et al., J Biol Chem 2004*, Milne et al., FEBS Lett 2004*
-
WikiPathways ESC Pluripotency Pathways:
AKT3/AKT2/AKT1
→
MDM2/MTOR
(activation)
-
WikiPathways Focal Adhesion-PI3K-Akt-mTOR-signaling pathway:
AKT1/AKT3/AKT2
→
MDM2
(activation)
-
WikiPathways Signaling Pathways in Glioblastoma:
AKT1/AKT2/AKT3
→
MDM2
(mim-stimulation)
-
WikiPathways Copper homeostasis:
AKT1
→
MDM2
(activation)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
-
IRef Bind_translation Interaction:
AKT1
—
MDM2
(experimental interaction detection)
Ashcroft et al., Oncogene 2002*
-
IRef Bind_translation Interaction:
AKT1
—
MDM2
(coimmunoprecipitation)
Ashcroft et al., Oncogene 2002*
-
IRef Biogrid Interaction:
AKT1
—
MDM2
(physical association, affinity chromatography technology)
Zhou et al., Nat Cell Biol 2001
-
IRef Biogrid Interaction:
AKT1
—
MDM2
(physical association, affinity chromatography technology)
Zhu et al., Oncogene 2011
-
IRef Biogrid Interaction:
AKT1
—
MDM2
(direct interaction, enzymatic study)
Milne et al., FEBS Lett 2004*
-
IRef Biogrid Interaction:
AKT1
—
MDM2
(physical association, affinity chromatography technology)
Deep et al., Oncogene 2008*
-
IRef Biogrid Interaction:
AKT1
—
MDM2
(physical association, affinity chromatography technology)
Lin et al., EMBO J 2002*
-
IRef Biogrid Interaction:
AKT1
—
MDM2
(physical association, affinity chromatography technology)
Kim et al., Exp Cell Res 2012*
-
IRef Biogrid Interaction:
AKT1
—
MDM2
(direct interaction, enzymatic study)
Ogawara et al., J Biol Chem 2002*
-
IRef Biogrid Interaction:
AKT1
—
MDM2
(direct interaction, enzymatic study)
Zhou et al., Nat Cell Biol 2001
-
IRef Dip Interaction:
AKT1
—
MDM2
(physical association, coimmunoprecipitation)
Lin et al., EMBO J 2002*
-
IRef Hprd Interaction:
AKT1
—
MDM2
(in vivo)
Mayo et al., Proc Natl Acad Sci U S A 2001, Lin et al., EMBO J 2002*, Milne et al., FEBS Lett 2004*
-
IRef Hprd Interaction:
AKT1
—
MDM2
(in vitro)
Mayo et al., Proc Natl Acad Sci U S A 2001, Lin et al., EMBO J 2002*, Milne et al., FEBS Lett 2004*
-
IRef Innatedb Interaction:
AKT1
—
MDM2
(unknown, -)
Mayo et al., Proc Natl Acad Sci U S A 2001
-
IRef Innatedb Interaction:
AKT1
—
MDM2
(unknown, -)
Feng et al., J Biol Chem 2004*
-
IRef Intact Interaction:
Complex of MDM2-GSK3B-AKT1
(association, anti bait coimmunoprecipitation)
Zhu et al., Oncogene 2011
-
IRef Intact Interaction:
AKT1
—
MDM2
(physical association, proximity ligation assay)
Liu et al., Mol Cell Proteomics 2013
-
IRef Intact Interaction:
AKT1
—
MDM2
(phosphorylation reaction, experimental interaction detection)
Milne et al., FEBS Lett 2004*
-
IRef Intact Interaction:
AKT1
—
MDM2
(phosphorylation reaction, protein kinase assay)
Wood et al., FEBS Lett 2009*
-
IRef Ophid Interaction:
AKT1
—
MDM2
(aggregation, interologs mapping)
Brown et al., Bioinformatics 2005
Text-mined interactions from Literome
Ogawara et al., J Biol Chem 2002
:
Both
Akt expression and serum treatment
induced phosphorylation of
Mdm2 at Ser186 ...
Akt mediated phosphorylation of
Mdm2 at Ser186 had little effect on the subcellular localization of Mdm2
Wrede et al., J Biol Chem 2002
(Necrosis) :
In addition, down-regulation of the pro-apoptotic tumor suppressor protein, p53, via
PKB mediated phosphorylation of
MDM2 might also play a role in partially protecting beta-cells from FFA induced apoptosis
Bárdos et al., Mol Cell Biol 2004
:
We found that growth factor stimulation, overexpression of
Akt/PKB , or loss of PTEN
resulted in enhanced expression of both HIF-1alpha and
HDM2
Mayo et al., J Biol Chem 2005
:
Induction of PTEN by p53 followed by expression of PTEN inhibits
AKT induced translocation of
MDM2 into the nucleus and sustains p53 function
Schmitz et al., Virchows Arch 2006
(Breast Neoplasms...) :
Besides the prognostic impact of pMDM2, our findings suggest that
Akt mediated modulation of the
MDM2/p53 complex contributes to increased tumour aggressiveness especially in p53 negative breast cancers
Wyszomierski et al., Cancer Cell 2005
(Neoplasm Metastasis) :
One possible mechanism for this surprising phenotype was that
Akt activated the E3 ubiquitin ligase
HDM2 , causing ubiquitination and degradation of NFAT, an invasion promoting factor
Limesand et al., Mol Cell Biol 2006
:
Dominant negative
Akt blocked phosphorylation of
MDM2 in salivary acinar cells from myr-Akt1 transgenic mice
Malmlöf et al., J Biol Chem 2007
:
Mdm2 is activated in
response to inhibited
Akt signaling ... In contrast, Ser-166 phosphorylation of
Mdm2 in lung cells was
mediated by
Akt
Groskreutz et al., J Immunol 2007
:
Mdm2 is
activated by
phospho-Akt , and we previously showed that RSV activates Akt and delays apoptosis in primary human airway epithelial cells
Cui et al., J Immunol 2008
:
Overexpression of a constitutively active FOXO3a increased DNA fragmentation with decreased cell viability in MDM, whereas a dominant negative mutant of FOXO3a or small interfering RNA for FOXO3a to knockdown the function of FOXO3a in HIV-1 infected MDM decreased DNA fragmentation and protected macrophages from death in HIV-1 infected MDM. Overexpression of constitutively active Akt-1 increased FOXO3a phosphorylation, suggesting that FOXO3a phosphorylation in human
MDM is
dependent on
Akt-1
Shankar et al., Oncogene 2008
:
Protein kinase C epsilon confers resistance of MCF-7 cells to TRAIL by
Akt dependent
activation of
Hdm2 and downregulation of p53 ... These results suggest that PKC epsilon mediates TRAIL resistance by
Akt mediated phosphorylation of
Hdm2 resulting in suppression of p53 expression and downregulation of Bid in MCF-7 breast cancer cells
Lopez-Pajares et al., J Biol Chem 2008
:
Previous studies have shown that
Akt phosphorylates and
stabilizes MDM2
Alam et al., Endocrinology 2009
:
These results indicate that FSH stimulated HIF-1 activation leading to up-regulation of targets such as vascular endothelial growth factor requires not only
PI3-kinase/AKT mediated activation of mammalian target of rapamycin as well as phosphorylation of FOXO1 and possibly
MDM2 but also a protein ( kinase ) activity that is inhibited by the classic ERK kinase inhibitor PD98059 but not ERK1/2 or 5
Jin et al., Biol Reprod 2009
:
The addition of Paf to the media caused increased phosphorylation of
MDM2 , and this was
blocked by inhibitors of phosphatidylinositol-3 kinase and
AKT
Takahashi et al., Exp Mol Pathol 2009
(Carcinoma, Squamous Cell...) :
Furthermore,
Akt expression
regulates Mdm2 expression, which may in turn regulate the function of wild-type p53
Gama et al., Cell Death Differ 2009
:
It is known that
Akt dependent phosphorylation of
Hdm2 causes nuclear translocation of Hdm2 followed by Hdm2 mediated inactivation of p53
Jin et al., Biol Reprod 2009
:
The addition of Paf to the media caused increased phosphorylation of
MDM2 , and this was
blocked by inhibitors of phosphatidylinositol-3 kinase and
AKT
Peirce et al., Cancer Chemother Pharmacol 2011
(Neuroblastoma) :
SF1126 blocks
MDM2 activation, IGF-1
induced activation of
Akt , and the upregulation of survivin induced by IGF-1
Hara et al., Nature 2011
:
In mice and in human cell lines, ß-arrestin-1 ( ARRB1 ), activated via ß ( 2 ) -adrenoreceptors, facilitates
AKT mediated activation of
MDM2 and also promotes MDM2 binding to, and degradation of, p53, by acting as a molecular scaffold
O'Neill et al., Theriogenology 2012
:
The
AKT induces the phosphorylation and activation of
MDM2 which causes the ubiquitination and resultant degradation of P53 resulting in the latency of P53 action
Christgen et al., Lab Invest 2012
(Breast Neoplasms...) :
These genes included CDKN1A,
MDM2 and PHLDA3, a recently described p53-inducible
inhibitor of
AKT
Singh et al., Cell Death Differ 2013
:
Inhibition of
MDM2 mediated
Akt phosphorylation with an Akt-phosphorylation-specific inhibitor abrogates its ability to improve cell survival
Hara et al., Cell cycle (Georgetown, Tex.) 2013
:
In this pathway, ß-arrestin-1, which is activated via ß 2ARs, facilitates the
AKT mediated activation of
Mdm2 and functions as a molecular scaffold to promote the binding and degradation of p53 by the E3-ubiquitin ligase, Mdm2
Lazrek et al., Neoplasia (New York, N.Y.) 2013
(Neoplasms) :
Anti-HER3 Domain 1 and 3 Antibodies Reduce Tumor Growth by Hindering HER2/HER3 Dimerization and
AKT Induced
MDM2 , XIAP, and FoxO1 Phosphorylation
Du et al., PloS one 2013
(Neoplasms) :
Additionally, it has been reported that
AKT can directly phosphorylate and
activate MDM2 ... In this study, we show that IGF-1 up-regulates
MDM2 protein levels in a
PI3K/AKT dependent manner