| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.83179434 |
| Akt physically associates with MDM 2 and phosphorylates it at Ser 166 and Ser 186 . 0.83179434^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Novel targets of Akt , p 21 ( Cipl / WAF1 ) , and MDM 2 . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.61867529 |
| In this study we show that HDM 2 associated with the serine threonine kinase , Akt , in response to growth factor stimulation of human primary cells . 0.61867529^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| We assessed whether the HDM 2 oncoprotein , a direct target of Akt / PKB , could regulate HIF 1alpha expression and HIF 1 activity under normoxic conditions . ^^^ We found that growth factor stimulation , overexpression of Akt / PKB , or loss of PTEN resulted in enhanced expression of both HIF 1alpha and HDM 2 . ^^^ Our study has important implications for the role of the PI 3K Akt / PKB HDM 2 pathway in tumor progression and angiogenesis . . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Vascular endothelial growth factor transcriptional activation is mediated by hypoxia inducible factor 1alpha , HDM 2 , and p70S6K1 in response to phosphatidylinositol 3 kinase / AKT signaling . ^^^ HDM 2 and p70S6K1 are two downstream targets of AKT that mediate growth factor induced VEGF transcriptional activation and HIF 1alpha expression . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Phosphorylation of HDM 2 on serine 166 by AKT has been shown to enhance HDM 2 activity and promote the degradation of p 53 . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Activated Akt expression in breast cancer : correlation with p 53 , Hdm 2 and patient outcome . ^^^ Activation of protein kinase B / Akt ( pAkt ) is mediated by oestrogen and involves HER 2 in vitro , to phosphorylate Hdm 2 and influence p 53 cytoplasmic localisation and degradation . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Specifically , signaling through Akt reduces NFAT expression levels due to ubiquitination and proteasomal degradation , mediated by the E 3 ubiquitin ligase HDM 2 . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| One possible mechanism for this surprising phenotype was that Akt activated the E 3 ubiquitin ligase HDM 2 , causing ubiquitination and degradation of NFAT , an invasion promoting factor . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Upon stimulation by IGF 1 , the Hdm 2 oncoprotein is phosphorylated by AKT , leading to its rapid nuclear translocation and subsequent inhibition of p 53 . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Rapamycin inhibited p70S6K1 , but not AKT activation , indicating that rapamycin affects HDM 2 phosphorylation via an AKT independent mechanism . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| A phosphatidylinositol 3 kinase / Akt pathway promotes translocation of Mdm 2 from the cytoplasm to the nucleus . ^^^ Mitogen induced activation of phosphatidylinositol 3 kinase ( PI 3 kinase ) and its downstream target , the Akt / PKB serine threonine kinase , results in phosphorylation of Mdm 2 on serine 166 and serine 186 . ^^^ Pharmacological blockade of PI 3 kinase / Akt signaling or expression of dominant negative PI 3 kinase or Akt inhibits nuclear entry of Mdm 2 , increases cellular levels of p 53 , and augments p 53 transcriptional activity . ^^^ Expression of constitutively active Akt promotes nuclear entry of Mdm 2 , diminishes cellular levels of p 53 , and decreases p 53 transcriptional activity . ^^^ Mutation of the Akt phosphorylation sites in Mdm 2 produces a mutant protein that is unable to enter the nucleus and increases p 53 activity . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| The PTEN tumor suppressor protein inhibits phosphatidylinositol 3 kinase ( PI3K ) / Akt signaling that promotes translocation of Mdm 2 into the nucleus . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Cross talk between Akt , p 53 and Mdm 2 : possible implications for the regulation of apoptosis . ^^^ On the other hand upon serum stimulation , when Akt becomes active and enhances cell survival , phosphorylation occurs at an Akt consensus site ( serine 166 ) within the Mdm 2 protein , a key regulator of p 53 function . ^^^ Taken together , our findings suggest that depending on the balance of signals , p 53 dependent downregulation of Akt may promote an irreversible commitment to apoptotic cell death , whereas effective recruitment of Akt by appropriate survival signals may lead to activation of Mdm 2 , inactivation of p 53 , and eventually inhibition of p 53 dependent apoptosis . . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Akt enhances Mdm 2 mediated ubiquitination and degradation of p 53 . p 53 plays a key role in DNA damage induced apoptosis . ^^^ Mdm 2 , a ubiquitin ligase for p 53 , plays a central role in regulation of the stability of p 53 and serves as a good substrate for Akt . ^^^ Both Akt expression and serum treatment induced phosphorylation of Mdm 2 at Ser 186 . ^^^ Akt mediated phosphorylation of Mdm 2 at Ser 186 had little effect on the subcellular localization of Mdm 2 . ^^^ However , both Akt expression and serum treatment increased Mdm 2 ubiquitination of p 53 . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Suppression of Rac 1 also induced apoptosis in 19 of 21 short term cultures of human primary cells from grades 2 and 3 oligodendroglioma and grade 4 glioblastoma that varied in p 53 , epidermal growth factor receptor , epidermal growth factor receptor 8 , MDM 2 , and p16 / p19 mutational or amplification status . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Mdm 2 can also bind to other cellular proteins such as hNumb , E2F1 , Rb and Akt ; however , the biological significance of these interactions is less clear . ^^^ Crosses did not reveal genetic interactions between Mdm 2 and the Drosophila homolog of E2F , Numb and Akt . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| In addition , combined TRAIL and wortmannin treatment resulted in cleavage of several proteins : PARP , Akt , p21 / WAF1 , and MDM 2 as well as dephosphorylation of Akt . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Southern blot and / or differential PCR analyses identified amplification of PDGFRA ( 4q12 ) , CCND 3 ( 6p21 ) , EGFR ( 7p12 ) , CDK 4 ( 12q14 ) and / or MDM 2 ( 12q14 . 3 q 15 ) , and AKT 1 ( 14q32 . 3 ) in the respective tumors . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Phosphorylation dependent ubiquitylation and degradation of androgen receptor by Akt require Mdm 2 E3 ligase . ^^^ Here we show that Akt and Mdm 2 form a complex with AR and promote phosphorylation dependent AR ubiquitylation , resulting in AR degradation by the proteasome . ^^^ The effect of Akt on AR ubiquitylation and degradation is markedly impaired in a Mdm 2 null cell line compared with the wild type cell line , suggesting that Mdm 2 is involved in Akt mediated AR ubiquitylation and degradation . ^^^ Furthermore , we demonstrate that the E 3 ligase activity of Mdm 2 and phosphorylation of Mdm 2 by Akt are essential for Mdm 2 to affect AR ubiquitylation and degradation . ^^^ These results suggest that phosphorylation dependent AR ubiquitylation and degradation by Akt require the involvement of Mdm 2 E3 ligase activity , a novel mechanism that provides insight into how AR is targeted for degradation . . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Similarly , Akt can block p 53 activation by potentiating Mdm 2 , whereas activated p 53 can tune down Akt in several different ways . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Recent observations show that phosphoinositide 3 kinase ( PtdIns 3 kinase ) Akt signaling promotes the phosphorylation and movement of the Mdm 2 oncoprotein into the nucleus , where it downregulates the p 53 tumor suppressor protein . ^^^ The PTEN tumor suppressor protein inhibits activation of Akt and this restricts Mdm 2 to the cytoplasm . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| In addition , down regulation of the pro apoptotic tumor suppressor protein , p 53 , via PKB mediated phosphorylation of MDM 2 might also play a role in partially protecting beta cells from FFA induced apoptosis . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Similarly , Akt can block p 53 activation by potentiating Mdm 2 , whereas activated p 53 can tune down Akt in several different ways . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Here we demonstrate that following a preconditioning protocol , the proapoptotic p 53 is inactivated possibly via phosphatidylinositol 3 kinase ( PI3K ) protein kinase B ( Akt ) murine double minute 2 ( Mdm 2 ) phosphorylation . ^^^ In conclusion our results suggest that p 53 is implicated in ischaemia / reperfusion injury and that preconditioning counterbalances this effect via PI3K Akt Mdm 2 phosphorylation . . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| We further demonstrate that cav 1 stimulated Akt activities lead to increased phosphorylation of multiple Akt substrates , including GSK 3 , FKHR , and MDM 2 . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Western blotting revealed no major change in the expression of the EGFR ligand transforming growth factor alpha of bcl 2 , bcl xL , p 53 , p 27 , MDM 2 , akt , activated phospho akt , or mitogen activated protein kinase . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| ZIP kinase was cloned , purified , and the enzyme was able to phosphorylate MDM 2 at Ser 166 , a site previously reported to be modified by Akt kinase , thus demonstrating that ZIP kinase is a bona fide MDM 2 binding protein . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Mdm 2 mRNA level is transcriptionally regulated by p 53 in response to stress such as DNA damage , and its protein level and subcellular localization are post translationally modulated by the AKT serine / threonine kinase . ^^^ Previous studies showed that PTEN , a dual specificity phosphatase that antagonizes phosphatidylinositol 3 kinase / AKT signaling , is capable of blocking MDM 2 nuclear translocation and destabilizing the MDM 2 protein . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Akt exerts its antiapoptotic function by its ability to phosphorylate many key components of the cellular apoptotic regulatory circuit , such as BAD , MDM 2 , FOXO Forkhead transcription factors , and PED ? ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Stabilization of Mdm 2 via decreased ubiquitination is mediated by protein kinase B / Akt dependent phosphorylation . ^^^ Here we show that PKB inhibits Mdm 2 self ubiquitination via phosphorylation of Mdm 2 on Ser ( 166 ) and Ser ( 188 ) . ^^^ Introduction of a constitutively active form of PKB together with Mdm 2 into cells induced phosphorylation of Mdm 2 at Ser ( 166 ) and Ser ( 188 ) and stabilized Mdm 2 protein . ^^^ In addition , activation of PKB correlated with Mdm 2 phosphorylation and stability in a variety of human tumor cells . ^^^ These findings suggest that PKB plays a critical role in controlling of the Mdm2 . p53 signaling pathway by regulating Mdm 2 stability . . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| A novel site of AKT mediated phosphorylation in the human MDM 2 onco protein . ^^^ Phosphorylation of MDM 2 by the protein kinase AKT is thought to regulate MDM 2 function in response to survival signals , but there has been uncertainty concerning the identity of the sites phosphorylated by AKT . ^^^ In the present study , we identify Ser 166 , a site previously reported as an AKT target , and Ser 188 , a novel site which is the major site of phosphorylation of MDM 2 by AKT in vitro . ^^^ Analysis of MDM 2 in cultured cells confirms that Ser 166 and Ser 188 are phosphorylated by AKT in a physiological context . . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Furthermore , unlike SDF 1 alpha , and independently of CD 4 , gp 120 ( IIIB ) is unable to stimulate Akt and some of its antiapoptotic targets ( NF kappa B and MDM 2 ) despite its ability to activate other signaling pathways in the same conditions . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| The tumors with negative MDM 2 staining showed a significantly high concordance of loss of Akt activity and low MDM 2 mRNA expression ( P < . 001 ) . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Adipocytes preexposed to TNF alpha for 5 h and then stimulated with insulin for 30 min exhibited decreased levels of Akt , phosphorylated Akt , as well as phosphorylated Mdm 2 , which is a known direct substrate of Akt , and glucose uptake . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Expression of cyclin D 1 , murine double minute 2 ( MDM 2 ) , and Akt was up regulated in tumors in comparison to normal mammary glands , as indicated by RT PCR , Western blot analysis , and immunohistochemical staining . ^^^ These data suggest that activation of cyclin D 1 , MDM 2 , and AKT as well as increased expression and cytoplasmic localization of p27Kip1 may play a role in this model of environmental pollutant induced mammary tumorigenesis . . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Examined apoptosis related genes included tumor suppressor genes p 53 , p 53 ; mouse double minute 2 , MDM 2 ; cyclin dependent kinase inhibitor p 21 ( WAF 1 ) , p 21 ( waf ) ; Bcl 2 associated protein 10 , BAX ; apoptotic protease activating factor 1 , Apaf 1 ; Caspase 9 and serine / threonine protein kinase , PKB . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Treatment of C 81 cells with LY 294002 resulted in an increase in the p 53 responsive gene MDM 2 , suggesting a role for AKT in the Tax mediated regulation of p 53 transcriptional activity . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Onzin overexpressing cells fail to induce p 53 in response to apoptotic stimuli and contain higher levels of the active , phosphorylated forms of Akt 1 and , more strikingly , of Mdm 2 . ^^^ Green fluorescent protein tagging also confirms directly that Akt 1 and Mdm 2 colocalize with onzin , although the precise subcellular distribution of each protein is dependent on its relative abundance . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Cell culture studies show that Akt related phosphorylation of MDM 2 at serine 166 allows MDM 2 to gain nuclear entry and fulfil its p 53 regulating function . ^^^ This study was designed to analyse the relationship of phospho MDM 2 ( pMDM 2 ) expression with Akt activation to determine a possible prognostic relevance of pMDM 2 in node negative breast cancer with respect to Akt activation and p 53 status . pMDM 2 , phospho Akt ( pAkt ) and p 53 protein expression status were analysed immunohistochemically in 121 paraffin embedded breast cancer cases . ^^^ These data confirm that MDM 2 phosphorylation at serine 166 is mediated by Akt kinase . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Tumors produced by subcutaneous injection of Akt transformed keratinocytes showed increased Foxo3a phosphorylation , but no major alterations in p 21 ( Cip1 / WAF1 ) , p 27 ( Kip 1 ) or mdm 2 expression and / or localization . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| The assay is capable of detecting significant effects of SNPs in two genes , MDM 2 and AKT 1 , whose products are involved in controlling the p 53 pathway and cellular response to DNA damage , suggesting that these data and this assay can be used to identify novel SNPs in other genes whose products impact the cellular response to radiation . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| The reduction of hAR protein is consistent with evidence that Wnt signaling increased phosphorylation of Akt and its downstream target , MDM 2 that promotes degradation of hAR protein through a proteasomal pathway . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Similarly , phosphorylated levels of three major targets of Akt and well known proapoptotic factors , the glycogen synthase kinase 3 ( GSK 3 ) , a Forkhead family member , FoxO 4 , and the protein murine double minute 2 ( MDM 2 ) , all inactivated upon phosphorylation by Akt , were decreased in preconditioned cells . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Previous studies showed that MDM 2 is an oncoprotein that controls tumorigenesis through both p 53 dependent and p 53 independent mechanisms , and tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 ( PTEN ) , a dual specificity phosphatase that antagonizes phosphatidylinositol 3 kinase ( PI 3K ) / AKT signaling , is capable of blocking MDM 2 nuclear translocation and destabilizing the MDM 2 protein . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| As a result of its interaction with and activation of Akt 1 and Mdm 2 , onzin down regulates p 53 . ^^^ PLSCR 1 interacts with the same cysteine rich domain of onzin as do Akt 1 and Mdm 2 , whereas the onzin interacting domain of PLSCR 1 centers around , but does not require , a previously identified palmitoylation signal . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| The presence of p Akt was accompanied by the phosphorylation of p 27 ( kip 1 ) , FRKHL 1 , MDM 2 , Bad , mTOR , and p70S6K . ^^^ Inhibition of the PI3K / Akt pathway in the MCL cell lines abrogated or reduced the phosphorylation of Akt , p 27 ( kip 1 ) , FRKHL 1 , MDM 2 , Bad , mTOR , GSK 3beta , IkappaB , and led to cell cycle arrest and apoptosis . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| Other studies showed the dysregulation of the expression of proteins involved in the control of cell cycle , proliferation , apoptosis , and invasiveness , such as Bcl 2 , Akt , mdm 2 , and epidermal growth factor receptor . ^^^ |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q00987 and P31749 |
Pubmed |
SVM Score :0.0 |
| NA |
|