| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :1.0875221 |
| Here we show that MDM 2 makes a functional contact with two cooperating transcription factors , E2F1 and DP 1 ( refs 4 , 5 ) , which are involved in S phase progression . 1.0875221^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.92887378 |
| MDM 2 constitutively binds to E2F 1 in all MM cells , to both wtp 53 and mtp 53 , and to p 21 in tumor cells lacking p 53 . 0.92887378^^^ |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.77960336 |
| There is also recent evidence which suggests that mdm 2 may play roles in p 53 independent pathways regulating cellular proliferation . mdm 2 has recently been shown to interact with the retinoblastoma tumor suppressor protein p ( Rb ) , and the E2F 1 and DP 1 transcription factors . 0.77960336^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.62652183 |
| Because MDM 2 also binds and activates the S phase specific transcription factor E2F1 , we hypothesized that increased E2F1 activity causes the development of the BLGmdm 2 phenotype . 0.62652183^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.54709251 |
| Direct binding between MDM 2 and E2F1 is necessary for the negative effects of MDM 2 on E2F1 ubiquitination , and deletion of the MDM 2 nuclear localization signal does not result in loss of the ability to increase the E2F1 protein level . 0.54709251^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| This function of E2F1 does not require its DP 1 binding , DNA binding , or transcriptional activity and is independent of mdm 2 . ^^^ |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| Retinoblastoma protein , c myc , and mdm 2 were unchanged , but E2F1 was down regulated . ^^^ |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| A mutational analysis of p 14 ( ARF ) indicates that the E2F 1 and MDM 2 binding domains can be distinguished . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| MDM 2 also interacts with the retinoblastoma protein ( RB ) and the transcription factor E2F1 to promote cell cycle S phase entry . ^^^ |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| In PC 3 cells , MDM 2 inhibition resulted in elevated p 21 , Bax , and pRb levels and decreased ppRb and E2F1 levels . ^^^ |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| MDM 2 inhibits tumor suppressor property of pRb , by releasing E2F1 , which stimulates DNA synthesis in S phase . ^^^ |
|
| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| The transcriptional activity of p 53 is known to be inhibited by the direct binding of mdm 2 , but we demonstrate here that both E2F1 and DP 1 can inhibit p 53 transcriptional activity independently of mdm 2 . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| Deletion of four residues from the E2F1 activation domain reduces CBP binding as well as transcriptional activation , but still allows the binding of RB and MDM 2 . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| Cleaved Rb bound cyclin D 3 and inhibited the transcriptional activity of E2F 1 , but failed to bind to the regulatory protein MDM 2 , which has been implicated in apoptosis . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| E2F1 induced apoptosis can be specifically inhibited by Rb but not mdm 2 , which is known for its ability to inhibit p 53 induced apoptosis . ^^^ The transactivation defective E2F1 mutants E2F1 ( 1 374 ) , E2F1 ( 390 1 ) DF ( delta mdm 2 ) , and E2F1 ( 406 415 ) ( delta Rb ) can induce apoptosis as effectively as wild type E2F1 . ^^^ This hypothesis was supported by our observation that although Rb overexpression can specifically repress the apoptosis induced by wild type E2F1 and a Rb binding competent E2F1 mutant E2F1 ( 390 1 ) DF ( delta mdm 2 ) , it failed to inhibit the apoptosis induced by mutants E2F1 ( 1 374 ) and E2F1 ( delta 406 415 ) ( delta Rb ) , which are defective or reduced in Rb binding and transactivation . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| E2F1 specific induction of apoptosis and p 53 accumulation , which is blocked by Mdm 2 . ^^^ We also find that coexpression of Mdm 2 , which is known to regulate p 53 activity , blocks the E2F1 mediated induction of apoptosis and also blocks the E2F1 mediated accumulation of p 53 . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| Expression of the cell cycle related proteins E2F 1 , p 53 , mdm 2 , p21waf 1 , and Ki 67 in multiple myeloma : correlation with cyclin D 1 immunoreactivity . ^^^ To explore other differences between cyclin D 1 positive and cyclin D 1 negative MMs , we assessed 59 MMs immunohistochemically for several G 1 cell cycle regulatory proteins , including cyclin D 1 , E2F 1 , p 53 , mdm 2 , and p21waf 1 , using routinely fixed and processed , paraffin embedded bone marrow specimens . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| Recently it has been shown that E2F 1 binds and coprecipitates with the mouse double minute chromosome 2 protein ( Mdm 2 ) . ^^^ A domain of E2F 1 ( amino acids 390 to 406 ) shows striking similarity to the Mdm 2 binding domain of the tumor suppressor protein p 53 . ^^^ Furthermore , microinjection of Mdm 2 antisense oligonucleotides upregulates E2F 1 protein , while microinjection of an unrelated oligonucleotide does not . ^^^ These data suggest that E2F 1 is upregulated in a similar way to p 53 in response to DNA damage and that Mdm 2 appears to play a major role in this pathway . . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| Adenovirus mediated E2F 1 gene transfer inhibits MDM 2 expression and efficiently induces apoptosis in MDM 2 overexpressing tumor cells . ^^^ MDM 2 also binds to the tumor suppressor pRB , as well as E2F 1 . ^^^ To investigate the effect of adenovirus mediated E2F 1 overexpression , MDM 2 overexpressing tumor cell lines were treated by mock infection , infection with an adenoviral vector expressing beta galactosidase , or E2F 1 ( Ad5CMV E2F 1 ) . ^^^ E2F 1 overexpression was associated with a marked decrease in MDM 2 levels and no evidence of increased Bax levels , whereas p 53 and Bcl 2 levels remained undetectable . ^^^ These results indicate that adenovirus mediated E2F 1 overexpression in MDM 2 overexpressing tumor cells results in decreased MDM 2 expression and widespread apoptosis . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| In addition to the interaction with p 53 , the MDM 2 protein has been found to have interactions with other cellular proteins such as pRb and E2F 1 . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| Induction of apoptosis in human esophageal cancer cells by sequential transfer of the wild type p 53 and E2F 1 genes : involvement of p 53 accumulation via ARF mediated MDM 2 down regulation . ^^^ Here we report that sequential transfer of the wild type p 53 and E2F 1 genes efficiently induces apoptosis in human esophageal cancer cells and that E2F 1 overexpression directly , activates expression of p 14 ( ARF ) , which inhibits MDM 2 mediated p 53 degradation , resulting in the stabilization of p 53 . ^^^ Tn and TE 8 with adenovirus vector expressing E2F 1 ( Ad E2F 1 ) enhanced mRNA and protein expression of ARF and decreased MDM 2 protein expression . ^^^ Moreover , Ad E2F 1 mediated ARF expression inhibited the up regulation of MDM 2 by overexpressed p 53 in TE 8 cells . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| The p 53 dependent pathway involves the induction by E2F 1 of the human tumour suppressor protein p14ARF , which neutralizes HDM 2 ( human homologue of MDM 2 ) and thereby stabilizes the p 53 protein . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| E2F1 , c Myc , and E1A mediated p 73 up regulation leads to activation of the p 73 transcription function , as shown by p 73 responsive reporter activity and by induction of known endogenous p 73 target gene products such as p 21 and HDM 2 . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| Moreover , we show that mdm 2 is required for the modulation of E2F1 activity by ARF . ^^^ Beside the well known p 53 and mdm 2 partners , these results identify E2F1 as a new ARF target . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| These functions are regulated by several factors including the E2F 1 binding protein MDM 2 and the retinoblastoma protein pRb . ^^^ Using a yeast two hybrid screen we have identified the MDM 2 related protein , MDMX , as an E2F 1 binding protein . ^^^ We also find that this transcriptionally inactive E2F 1 mutant is capable of degrading the MDMX related protein MDM 2 and the MDMX isoform MDMX S . ^^^ Mapping of the E2F 1 C terminus reveals that neither a previously characterized C terminal MDM 2 binding domain nor the pRb binding domain on E2F 1 is required for MDMX and MDM 2 degradation . . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| In this study , CD 95 induced cleavage of the G1 / S checkpoint regulator proteins , retinoblastoma protein ( pRb ) and murine double minute 2 ( mdm 2 ) , was associated with an increased protein concentration of a key transcription factor , E2F 1 , which is regulated by both of them . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| Expression by recombinant adenovirus of E2F1 , E2F2 , E2F3 , cyclin E / cdk2 , and Mdm 2 individually resulted in DNA synthesis in 10 30 % of cells . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| MTT mdm 2 cells show high levels of E2F 1 protein , suggesting that the induction of apoptosis observed upon MDM 2 overexpression could be dependent on E2F 1 . ^^^ This observation is further supported with assays showing that E2F 1 binding to specific DNA sequences is enhanced in MTT mdm 2 cells . ^^^ Likewise , transactivation of reporter constructs exclusively dependent on E2F 1 is also elevated after transfection with MDM 2 . ^^^ We conclude that the effects observed by MDM 2 overexpression could be mediated by E2F 1 . . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
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 . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| These phenotypes in the mammary epithelia of the transgenic mice are not dependent on either p 53 or the transcription factor E2F1 , as mice null for these genes carrying the BLGmdm 2 transgene exhibit similar defects to mice carrying the BLGmdm 2 transgene alone . p19ARF , an alternative splice product of the INK4a / ARF locus , has been shown to interact directly with MDM 2 . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| Mdm 2 inhibition of p 53 induces E2F1 transactivation via p 21 . ^^^ In addition to regulation of p 53 , Mdm 2 has been reported to stimulate E2F1 transactivation by a mechanism that remains unclear . ^^^ Here we examined how overexpression of Mdm 2 alters E2F1 / DP1 transactivation . ^^^ Using a set of cell lines with differing p 53 and Rb status we determined that Mdm 2 induction of E2F1 transactivation was p 53 dependent , resulting from release of repression by p 53 . ^^^ While Mdm 2 association with p 53 was required to increase E2F1 transactivation , Mdm 2 mediated degradation of p 53 was not . p 53 repression of E2F1 transactivation required a functional DNA binding and transactivation domain . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| In view of this dichotomy in its functions and its critical role in cell cycle control , this study examined the following four aspects of E2F 1 in a panel of 87 non small cell lung carcinomas ( NSCLCs ) , previously analysed for defects in the pRb p 53 MDM2 network : firstly , the status of E2F 1 at the protein , mRNA and DNA levels ; secondly , its relationship with the kinetic parameters and genomic instability of the tumours ; thirdly , its association with the status of its transcriptional co activator CBP , downstream target PCNA and main cell cycle regulatory and E2F 1 interacting molecules pRb , p 53 and MDM 2 ; and fourthly , its impact on clinical outcome . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| The most important finding in our study , was the correlation of nuclear beta cat immunohistochemical localization with increased proliferation , overexpression of E2F1 and MDM 2 , aberrant p 53 , and low expression of p 27 ( KIP ) , providing for the first time in vivo evidence that beta cat associated proliferation correlates with release of E2F1 activity and loss of p 53 and p 27 ( KIP ) dependent cell cycle checkpoints . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| Expression array analysis of 23 cell cycle related genes showed that IFN gamma inhibited EGF induced increases in E2F 1 expression , whereas induction of c myc , cyclin D 2 , Egr 1 , and mdm 2 were unaffected . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| Both Myc and E2F1 activation rapidly induced p 53 phosphorylation at Ser 15 , p 53 protein accumulation , and upregulation of the p 53 target genes MDM 2 and p 21 . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| Our data show a significant transcriptional activation of E2F 1 in primary rat hepatocytes incubated with TGF beta 1 , as well as a 5 fold increase in p 53 and a 2 fold decrease in its inhibitor , Mdm 2 ( p < 0 . 05 ) . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| METHODS : Using a streptavidin biotin method , five cases of SDC were evaluated immunohistochemically for the presence of cyclin D 1 , CDK 4 ( cyclin dependent kinase 4 ) , p 16 ( CDK2A ) , pRb ( retinoblastoma protein ) , E2F 1 , p 53 , mdm 2 ( murine double minute 2 ) , bcl 2 , and the c erbB 2 oncoprotein to determine whether there was a correlation between the expression of these proteins and patient outcome . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| While examining the effect of Mdm 2 overexpression on E2F1 transactivation we uncovered a novel MdmX function , the ability to inhibit E2F1 transactivation in a p 53 and Mdm 2 independent manner . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| In PC 3 cells that are p 53 null , after inhibition of MDM 2 expression , Bax and p 21 levels were elevated , and E2F1 levels were decreased . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| Our results demonstrated that 16 genes ; bad , bax , bcl 2 , bcl w , bcl 10 , caspase 3 , caspase 7 , caspase 8 , c myc , E 124 , GADD 45 , mdm 2 , NKkappab 1 , p 53 , p 21 , Rb and trail were up regulated and six genes ; caspase 1 , caspase 2 , DR 5 , E2F1 , FasL and iNOS did not changed in response to DES treatment in wild type mice compared to p53+ / knockout mice . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| In particular , we demonstrate that p14ARF interacts with the SUMO E 2 conjugating enzyme , Ubc 9 and enhances the sumoylation of its binding partners , hdm 2 , E2F 1 , HIF 1alpha , TBP 1 and p120E4F . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| Recently , an E2F1 mutant lacking the DNA binding domain , E2F1 ( 180 437 ) , has been implicated in degradation of MDMX and MDM 2 proteins via lysosomal proteases . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| EXPERIMENTAL DESIGN : We determined the mRNA expression of p 1 ( INK4A ) , p 14 ( ARF ) , CDK 4 , RB 1 , MDM 2 , TP 53 , and E2F1 by quantitative reverse transcription PCR in 38 cases of GISTs and correlated the findings with clinicopathologic factors , including mutation analysis of KIT and PDGFRA . ^^^ GISTs with low mRNA expression of the CDKN2A transcripts p 16 ( INK4A ) and p 14 ( ARF ) but high mRNA expression of CDK 4 , RB 1 , MDM 2 , TP 53 , and E2F1 were associated with aggressive clinical behavior and unfavorable prognosis , whereas GISTs with a low mRNA expression of CDK 4 , RB 1 , MDM 2 , TP 53 , and E2F1 were not . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| MDM 2 is an E 3 ubiquitin ligase that regulates the proteasomal degradation and activity of proteins involved in cell growth and apoptosis , including the tumor suppressors p 53 and retinoblastoma and the transcription factor E2F1 . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| This article summarizes the biochemical and molecular studies of the role of MDM 2 in the regulation of p 21 and E2F1 expression , stability and function , providing evidence for the utility of RNA silencing technologies , including antisense oligonucleotides and siRNAs . . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| Involvement of the transcriptional factor E2F1 in the regulation of the rRNA promoter . p16INK4a pRB E2F and ARF MDM 2 p53 are two major tumor suppressor networks involved in cell proliferation control . ^^^ The nucleolar ARF protein binds to MDM 2 to activate the growth suppressive functions of p 53 , but can also exert its tumor suppressor activity independently of p 53 , through mechanisms involving other regulators : in that manner , p14ARF has been shown to inhibit the transcriptional activity of E2F1 in vitro , suggesting that the two pathways intersect with one another . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| Immunohistochemical stains were carried out on tissue microarrays to evaluate the expression of proteins involved in the G ( 1 ) S transition and proteins that regulate apoptosis including Rb , E2F1 , cyclin D 1 , CDK 4 , CDK 6 , p 27 ( KIP 1 ) , p 21 ( WAF1 / CIP1 ) , p 53 , Mdm 2 , Bcl 2 , and Bax . ^^^ The positive phenotypes identified were as follows : Rb , 39 . 1 % ; E2F1 , 69 . 6 % ; cyclin D 1 , 30 . 4 % ; CDK 4 , 100 % ; CDK 6 , 30 . 4 % ; 39 . 1 % ; p 27 ( KIP 1 ) , 47 . 8 % ; p 21 ( WAF1 / CIP1 ) , 39 . 1 % ; p 53 , 43 . 5 % ; Mdm 2 , 17 . 4 % ; Bcl 2 , 91 . 3 % ; and Bax , 100 % . ^^^ |
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| Interacting proteins: Q01094 and Q00987 |
Pubmed |
SVM Score :0.0 |
| Taken together , our data demonstrate that the response of p 53 null cells to ARF is cell type dependent and involves factors other than Mdm 2 and E2F1 . . ^^^ |
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