| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :1.2079996 |
| In this context , we demonstrate that ARF interacts physically with E2F1 and inhibits its transcriptional activity . 1.2079996^^^ Human ARF binds E2F1 and inhibits its transcriptional activity . 0.57834357^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Expression of p14ARF did not change after E2F 1 infection in either cell line . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
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 . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Alterations of p14ARF , p 53 , and p 73 genes involved in the E2F 1 mediated apoptotic pathways in non small cell lung carcinoma . ^^^ Overexpression of E2F 1 induces apoptosis by both a p14ARF p 53 and a p 73 mediated pathway . p14ARF is the alternate tumor suppressor product of the INK4a / ARF locus that is inactivated frequently in lung carcinogenesis . ^^^ These data are consistent with the current model of p14ARF and p 53 interaction as a complex network rather than a simple linear pathway and indicate a possible role for an E2F 1 mediated failsafe , p 53 independent , apoptotic pathway involving p 73 in human lung carcinogenesis . . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Myc and E2F1 induce p 53 through p14ARF independent mechanisms in human fibroblasts . p19ARF is induced in response to oncogene activation or during cellular senescence in mouse embryo fibroblasts , triggering p 53 dependent and p 53 independent cell cycle arrest and apoptosis . ^^^ We have studied the involvement of human p14ARF as a regulator of p 53 activity in normal human skin fibroblasts ( NHFs ) or WI 38 lung embryonic fibroblasts expressing conditional Myc or E2F1 estrogen receptor fusion proteins . ^^^ Activation of E2F1 induced p14ARF mRNA and protein levels . ^^^ Myc and E2F1 induced p 53 and cell cycle arrest even after silencing of p14ARF using short interfering RNA . ^^^ Our results indicate that p 53 phosphorylation , but not p14ARF , plays a major role for the induction of p 53 in response to Myc and E2F1 activation in normal human fibroblasts . . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| These results suggest that elevated MdmX expression may repress E2F1 regulated genes like p14ARF and thus represent another regulatory mechanism in the Rb p 53 signaling pathway . . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Furthermore , p 53 , p14ARF , c myc and E2F1 , but not E1A , induced p53S15 phosphorylation was substantially reduced in AT fibroblasts ( GM 05823 ) . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
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 . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| ARF targets certain E2F species for degradation . p19ARF suppresses the growth of cells lacking p 53 through an unknown mechanism . p19ARF was found to complex with transcription factors E2F1 , 2 , and 3 . ^^^ Levels of endogenous or ectopically expressed E2F1 , 2 , and 3 , but not E2F6 , were reduced after synthesis of p19ARF , through a mechanism involving increased turnover . p19ARF induced degradation of E2F1 depended on a functional proteasome , and E2F1 was relocalized to nucleoli when coexpressed with p19ARF . ^^^ Consistent with reduced levels of E2F1 and E2F3 , the proliferation of cells defective for p 53 function was suppressed by p19ARF , and the effect was partially reversed by ectopic overexpression of E2F1 . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
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 . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| It has been proposed that the E2F1 transcription factor serves as a link between the Rb / E2F proliferation pathway and the p 53 apoptosis pathway by inducing the expression of p19ARF , a protein that regulates p 53 stability . ^^^ We find that although p19ARF contributes to p 53 accumulation in response to E2F expression , p19ARF is not required for E2F1 mediated apoptosis . ^^^ E2F1 can signal p 53 phosphorylation in the absence of p19ARF , similar to the observed modifications to p 53 in response to DNA damage . ^^^ These modifications are not observed in the absence of p19ARF following expression of E2F2 , an E2F family member that does not induce apoptosis in mouse embryo fibroblasts but can induce p19ARF and p 53 protein expression . p 53 modification is found to be crucial for E2F1 mediated apoptosis , and this apoptosis is compromised when E2F1 is coexpressed with a p 53 mutant lacking many N and C terminal phosphorylation sites . ^^^ These findings suggest that p 53 phosphorylation is a key step in E2F1 mediated apoptosis and that this modification can occur in the absence of p19ARF . . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Moreover , the apoptotic efficacy of 5 aza dC is proprietary of p 53 deficient cells , not being observed in cells lacking other cell cycle regulators , such as p19ARF , p16INK4a , p 21 ( CIP1 / WAF1 ) , E2F 1 , or E2F 2 . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Moreover , D type cyclin dependent kinase activity specifically activates the E2F 1 promoter by relieving E2F mediated repression but is inhibited by coexpression of the cdk 4 and cdk 6 inhibitor p 16 ( CDKN 2 , MTS 1 , INK 4 ) . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Here we present evidence that activation of a cAMP pathway correlates with multiple cellular changes in these cells : ( 1 ) increased expression of the transcription factor microphthalmia ; ( 2 ) increased melanogenesis ; ( 3 ) increased association of the cyclin dependent kinase inhibitors ( CDK Is ) p 27 ( KIP 1 ) and p 16 ( INK 4 ) with CDK 2 and CDK 4 , respectively ; ( 4 ) failure to phosphorylate the retinoblastoma protein ( pRB ) ; ( 5 ) decreased expression of E2F1 , E2F2 , and E2F4 proteins ; ( 6 ) loss of E2F DNA binding activity ; and ( 7 ) phenotypic changes characteristic of senescent cells . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Indeed , when Tax is coexpressed with the E2F 1 transcription factor in CEM T cells , which lack expression of p 16 ( INK4A ) , it strongly potentiates the E2F dependent activation of a reporter construct driven by a promoter containing E2F binding sites . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Protein levels of p 21 ( WAF 1 ) , p 16 ( INK4a ) , p 53 , pRb ( retinoblastoma protein ) , and E2F 1 were not changed . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Deregulated E2F 1 blocks terminal differentiation and loss of leukemogenicity of M 1 myeloblastic leukemia cells without abrogating induction of p 15 ( INK4B ) and p 16 ( INK4A ) . ^^^ Although E2F 1 blocked IL 6 mediated terminal differentiation and its associated growth arrest , it did not prevent the rapid induction of both p 15 ( INK4B ) and p 16 ( INK4A ) , inhibition of cdk 4 kinase activity , and subsequent hypophosphorylation of pRb . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Using immunohistochemistry , patterns of expression of pRB , p16 / INK4A , and E2F1 were analyzed in tissue from a cohort of 86 well characterized patients with nonfamilial retinoblastoma diagnosed at the `` Instituto Nacional de Pediatria ' ' in Mexico City . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Induction is mediated through ARF , an alternative reading frame product of the INK4A tumor suppressor locus , in a manner partially dependent on the transcription factor E2F1 . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| In nodules and / or HCCs of Wistar and BN rats , low or no increases in c myc , Cyclins D 1 , E , and A , and E2F1 expression , and Cyclin CDKs complex formation were associated with p 16 ( INK4A ) overexpression and pRb hypophosphorylation . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| While expression of the genes for cyclin D 1 , CDK 4 , and E2F1 increased in lung adenocarcinomas relative to normal lung , expression of p 15 ( Ink4b ) , p 16 ( Ink4a ) , p 21 ( Cip 1 ) , p 27 ( Kip 1 ) , p 57 ( Kip 2 ) , and pRb genes decreased in comparison . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| There was also a decrease in the expression of hyper phosphorylated retinoblastoma protein , the transcription factor E2F1 , and proliferating cell nuclear antigen , and there was an increase in expression of hypophosphorylated Rb and the cdk inhibitor p 16 ( Ink4a ) with increasing p 75 ( NTR ) expression . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| The relationships between E2F 1 or pRb expression and outcome were assessed by univariate and multivariate Cox ' s proportional hazards model , with or without clinicopathological covariates , including nodal status , disease stage , treatment status , and molecular markers ( cyclin D 1 , p 16 ( INK4A ) , and Ki 67 ) previously measured in this cohort . ^^^ However , when considered simultaneously with other significant factors , i . e . lymph node status , p 16 ( INK4A ) protein expression , and histopathological grade , in the multivariate Cox ' s proportional hazards model , the additional contributions of E2F 1 and / or pRb expression to DFS and OS were not statistically significant . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| To assess the cellular mechanisms underlying the mesangial cell proliferation and glomerulosclerosis in progressive human IgA nephropathy ( IgAN ) , we examined the expression of E2F1 , Rb , c Myc , proliferating cell nuclear antigen ( PCNA ) , cyclins ( D 1 , E and A ) , cyclin dependent kinase 2 ( CDK 2 ) and CDK inhibitors ( p 21 ( waf 1 ) , p 27 ( kip 1 ) , 57 ( kip 2 ) and p 16 ( ink4a ) ) by immunohistochemistry in renal biopsy specimens . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Overexpression of both viral proteins induces cellular proliferation , retinoblastoma ( pRb ) phosphorylation , and accumulation of products of genes that are negatively regulated by pRb , such as p 16 ( INK4a ) , CDC 2 , E2F 1 , and cyclin A . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Using univariate and multivariate Cox ' s proportional hazards models , the outcomes examined were time to disease recurrence or death , with or without clinicopathologic covariates , including nodal status , disease stage , treatment status , Ki 67 staining , and molecular markers with known functional or genetic relationships with p 14 ( ARF ) ( p 16 ( INK4A ) , p 53 , pRb , p 21 ( WAF1 / CIP1 ) , E2F 1 ) . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
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 . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| These basal , E2F1 associated DSBs are not observed in a p 16 ( ink4a ) inactivated cancer cell line that retains functional pRb , unless pRb is depleted . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Analysis of mRNA expression revealed that SC 1 cells treated with 50 microg of CEE / mL had lower levels of the p 16 ( INK4a ) alternate reading frame sequence ( ARF ) and E2F 1 than untreated SC 1 cells . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| The ARF promoter was also found to be highly responsive to E2F1 expression , in keeping with previous results at the RNA level . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Unlike genes such as Myc , adenovirus E1A , and E2F 1 , which , when overexpressed , activate the ARF p 53 pathway and trigger apoptosis , DMP 1 , like ARF itself , does not induce programmed cell death . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Regulation of a senescence checkpoint response by the E2F1 transcription factor and p 14 ( ARF ) tumor suppressor . ^^^ The E2F1 target gene critical for the senescence response appeared to be the p 14 ( ARF ) tumor suppressor . ^^^ Replicatively senescent human fibroblasts overexpressed p 14 ( ARF ) , and ectopic expression of p 14 ( ARF ) in presenescent cells induced a phenotype similar to that induced by E2F1 . ^^^ Consistent with a critical role for p 14 ( ARF ) , cells with compromised p 53 function were immune to senescence induction by E2F1 , as were cells deficient in p 14 ( ARF ) . ^^^ Our findings support the idea that the senescence response is a critical tumor suppressive mechanism , provide an explanation for the apparently paradoxical roles of E2F1 in oncogenesis , and identify p 14 ( ARF ) as a potentially important mediator of the senescent phenotype . . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| A role for E2F1 in the induction of ARF , p 53 , and apoptosis during thymic negative selection . ^^^ This T cell receptor mediated apoptosis coincides with the E2F1 dependent increase of p 19 ARF mRNA and p 53 protein levels . ^^^ These results demonstrate a specific role for E2F1 , which triggers a pathway leading to ARF and p 53 induction , in a physiological apoptosis pathway that is uncoupled from a normal proliferative event . . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| ARF is induced by activated oncogenes sucll as c myc , E1A and E2F 1 . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Unlike E2F1 , E2F4 does not induce apoptosis , and this correlates with the differential abilities of these two E2F species to stimulate p 19 ( ARF ) expression in vivo . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
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 . ^^^ Thus , overexpression of ectopic E2F 1 protein may stabilize endogenous as well as ectopic p 53 protein via the E2F 1 / ARF / MDM2 / p53 regulatory pathway and , in this way , render cells more sensitive to apoptosis , an outcome that has important implications for the treatment of human esophageal cancers . . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| TBX 2 represses the Cdkn2a ( p 19 ( ARF ) ) promoter and attenuates E2F1 , Myc or HRAS mediated induction of Cdkn2a ( p 19 ( ARF ) ) . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| E2F1 mediated neuronal apoptosis did not require activation of gene transcription because : ( 1 ) ectopic expression of E2F1 or its mutants lacking the transactivation domain induced neuronal apoptosis , whereas an E2F1 mutant lacking the DNA binding domain did not ; ( 2 ) under all of these conditions , known E2F1 target genes including cyclin A , cdc 2 and p 19 ( ARF ) were not induced ; and ( 3 ) DA evoked neuronal apoptosis was associated with up regulated E2F1 , but not transcription of its target genes . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| E2F 1 up regulates c Myc and p 14 ( ARF ) and induces apoptosis in colon cancer cells . ^^^ Of mechanistic importance , overexpression of E2F 1 caused a G ( 2 ) / M arrest followed by increased levels of c Myc and p 14 ( ARF ) proteins . ^^^ Overexpression of E2F 1 triggers apoptosis and is associated with up regulation of c Myc and p 14 ( ARF ) proteins and down regulation of Mcl 1 . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| We further showed that E2F1 , a transcription factor known to induce p 19 ( ARF ) expression , was required for the response . ^^^ Here , we use a genetic approach to test whether p 19 ( ARF ) functions to transduce the signal from E2F1 to p 53 in this tumor suppression pathway . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| ARF differentially modulates apoptosis induced by E2F1 and Myc . ^^^ The finding that E2F1 transcriptionally regulates the ARF gene has led to the suggestion that ARF contributes to E2F1 induced apoptosis . ^^^ Counter to this hypothesis , this study demonstrates not only that ARF is unnecessary for E2F1 to induce apoptosis but also that inactivation of ARF actually enhances the ability of E2F1 to promote apoptosis . ^^^ Inactivation of ARF also cooperates with E2F1 activity to promote entry into the S phase of the cell cycle . ^^^ This relationship between ARF and E2F1 is demonstrated in transgenic epidermis in vivo and in mouse embryo fibroblast cultures in vitro . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| In common with other E2F1 responsive genes such as p 14 ( ARF ) and B myb , the promoter of p 73 is shown to be positively regulated in cell lines and primary human keratinocytes by E 7 proteins from oncogenic human papillomavirus ( HPV ) types 16 , 18 , 31 and 33 , but not HPV 6 . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Transcriptional regulation of the human tumor suppressor p 14 ( ARF ) by E2F1 , E2F2 , E2F3 , and Sp 1 like factors . ^^^ A variety of mitogenic stimuli upregulate ARF but a direct modulation at the transcriptional level has been reported only for E2F 1 . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Activation of ARF by oncogenic stress in mouse fibroblasts is independent of E2F1 and E2F2 . ^^^ Notably , ectopic expression of E2F1 upregulates ARF transcriptionally , and both E2F1 and ARF have been implicated in apoptosis and cell cycle arrest . ^^^ We have used primary mouse fibroblasts deficient for E2F1 , E2F2 , or both to determine the possible role of these E2F proteins as upstream regulators of ARF in response to oncogenic stimuli and other stresses . ^^^ None of the ARF mediated responses that we have analysed is significantly affected in E2F1 ( / ) , E2F2 ( / ) or E2F1 / 2 ( / ) MEFs , and ARF is upregulated normally in all cases . ^^^ Taken together , our results indicate that the activation of ARF in response to oncogenic stress can occur by E2F1 and E2F2 independent mechanisms . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
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 . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| To date only p 14 ( ARF ) and p 73 , a p 53 homologue , have been identified as E2F 1 inducible genes capable of mediating an apoptotic response . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| We show that K cyclin expression in primary cells sensitizes to apoptosis and induces growth arrest , both of which are dependent on p 53 but independent of E2F1 or p 19 ( ARF ) . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Differential regulation of E2F1 , DP 1 , and the E2F1 / DP1 complex by ARF . ^^^ For example , it has been shown that ARF induces proteolysis of certain E2F species , including E2F1 . ^^^ In addition , ARF relocalizes E2F1 from the nucleoplasm to nucleolus and inhibits E2F1 activated transcription . ^^^ Surprisingly , however , the E2F1 / DP1 complex is refractory to ARF regulation . ^^^ Coexpression of E2F1 and DP 1 blocks ARF induced relocalization of either subunit to the nucleolus . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Induction of p 14 ( ARF ) on confluency occurred with low E2F 1 levels . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Expression of ARF is up regulated in response to a number of oncogenic stimuli including E2F1 . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| As a transcriptional target of E2F 1 , a regulator of p 53 , and an important mediator of apoptosis , ARF was a strong candidate for such a role , especially since it can be upregulated in the absence of Rb . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| In contrast , Myc induced apoptosis and the frequency of Arf and p 53 mutations in lymphomas were unaffected by E2f1 loss . ^^^ Therefore , Myc does not require E2f1 to induce Arf , p 53 , or apoptosis in B cells , but depends upon E2f1 to accelerate cell cycle progression and downregulate p 27 ( Kip 1 ) . . ^^^ |
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| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Using a transactivation defective E2F1 mutant , we show that apoptosis induction is independent of the transactivation function and therefore independent of ARF and p 73 . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| In an effort to address the underlying molecular mechanism of the resistance of E2F1 null mice , the expression of several downstream proapoptotic target genes ( p 73 , Apaf 1 , Arf ) of the E2F1 transcription factor was measured by quantitative polymerase chain reaction . ^^^ |
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| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| E2F1 / DP1 induces the expression of ARF , which in turn blocks MDM 2 mediated ubiquination of p 53 . ^^^ E2F1 / DP1 , however , can mediate p 53 dependent apoptosis in the absence of ARF through the upregulation of the p 53 kinase ATM and by E2F1directly binding to p 53 , which enhances p 53 transcriptional activity . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Specifically , we observe recruitment of the endogenous activating E2Fs , E2F1 , and E2F3a , to the Arf promoter . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Surprisingly , the promoter of the p 14 ( ARF ) gene , which was also activated by E2F 1 , became repressed by EAPP . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| The time course of E2F1 induction was observed at 6 24 h , and it was found to precede p 19 ( ARF ) expression . ^^^ In MDCK cells , the overexpression of E2F1 increased promoter activity and the protein level of p 19 ( ARF ) and induced apoptosis . ^^^ CONCLUSIONS : These data support the hypothesis that the E2F1 p 19 ( ARF ) p 53 pathway forms a negative feedback loop to regulate the cell cycle of renal tubular cells in the ischemic ARF . . ^^^ |
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| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Western blot analysis revealed that LNCaP E2F1 cells have elevated expression of p 73 , Apaf 1 , caspase 3 , caspase 7 , but expression of caspase 8 and 9 , p 14 ( ARF ) , and Mcl 1 , is unaltered . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Interestingly , binding of ARF to DP 1 results in an inhibition of the interaction between DP 1 and E2F1 . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| The downregulation of E2F1 upon MDM 2 inhibition was not due to either pRB or p 14 ( Arf ) . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| E2F1 suppresses skin carcinogenesis via the ARF p 53 pathway . ^^^ E2F1 transgenic epidermis displayed increased expression of p 19 ( ARF ) , p 53 , and p 21 ( Cip 1 ) . ^^^ Inactivation of either p 53 or Arf in E2F1 transgenic mice restored sensitivity to two stage skin carcinogenesis . ^^^ While Arf inactivation impaired tumor suppression and p 21 induction by E2F1 , it did not reduce the level of apoptosis observed in E2F1 transgenic mice . ^^^ Based on these findings , we propose that E2F1 suppresses ras driven skin carcinogenesis through a nonapoptotic mechanism involving ARF and p53 . . ^^^ |
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| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Although it has been well documented that E2F1 is able to induce p 53 dependent apoptosis via raising ARF activity , the mechanism by which E2F induces p 53 independent apoptosis remains unclear . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Furthermore , ectopic expression of p 14 ( ARF ) did not lead to degradation of the E2F1 protein and did not result in the reduction of E2F1 activity detected by two E2F1 responsible promoters , Apaf 1 and p 14 ( ARF ) promoter , in 293T , p 53 ( / ) HCT 116 , and H 1299 cells . ^^^ 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 . . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| In response to oncogenic stress , the activating E2Fs , E2F1 , 2 , and E2F3A , all associate with Arf and promote its transcription . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Furthermore , the pRB associated E2Fs were all able to overcome a G 1 arrest mediated by the p16INK4 tumor suppressor protein , and E2F 1 was shown to override a G 1 block mediated by a neutralizing antibody to cyclin D 1 . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Expression of p16Ink4 , which specifically inhibits cyclin D directed cdks , blocks cells in G 1 phase ; this block can be overcome by expression of the viral proteins that inactivate pRb or by E2F 1 . ^^^ |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Whereas , upon overexpression , E2F 1 , 2 , and 3 induce S phase in quiescent fibroblasts and override G 1 arrests mediated by the p16INK4A tumor suppressor protein or neutralizing antibodies to cyclin D 1 , E2F 4 and 5 do not . ^^^ |
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| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Using a combination of gene disruption and ectopic expression in growth factor dependent mouse melanocytes , we studied the roles of E2F1 and the p16INK4A and p21WAF1 / CIP1 CKIs ( cyclin dependent kinase inhibitors ) in the acquisition of TPA ( 12 O tetradecanoyl phorbol 13 acetate ) independent growth in culture , a hallmark of melanomas . ^^^ |
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| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Frequent disruption of the RB 1 pathway in diffuse large B cell lymphoma : prognostic significance of E2F 1 and p16INK4A . ^^^ Low E2F 1 expression was associated with treatment failure ( P = 0 . 020 ) , and multivariate analysis of overall survival identified both low E2F 1 expression ( relative risk = 6 . 9 ; P = 0 . 0037 ) and p16INK4A inactivation ( relative risk = 3 . 3 ; P = 0 . 0247 ) as independent prognostic markers . ^^^ Furthermore , low E2F 1 expression and p16INK4A inactivation may serve as prognostic markers for patients with this type of lymphoma . . ^^^ |
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| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Melanin accumulation accelerates melanocyte senescence by a mechanism involving p16INK4a / CDK4 / pRB and E2F1 . ^^^ Here we demonstrate that in melanocytes derived from dark skinned individuals , CT induced melanogenesis is associated with accumulation of the tumor suppressor p16INK4a , underphosphorylated retinoblastoma protein ( pRb ) , downregulation of cyclin E , decreased expression of E2F1 , and loss of E2F regulated S phase gene expression . ^^^ |
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| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Exogenous wild type p16INK4A gene induces delayed cell proliferation and promotes chemosensitivity through decreased pRB and increased E2F 1 expressions . ^^^ |
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| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| In DLCL , both p16INK4A inactivation and reduced E2F 1 expression conferred shortened survival . p 53 alteration was associated with poor prognosis of both B cell and , especially , T cell lymphoma . ^^^ |
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| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| To confirm the role of cell cycle deregulation in human fetal nasopharyngeal epithelial cells escaping from the replicative senescence induced by Epstein Barr virus infection , we detected expression of cell cycle regulators , such as p16INK4a , p21WAF1 / CIP1 , p 53 , and E2F1 with Western blotting and immunocytochemisty in this study . ^^^ Our results found that Epstein Barr virus inhibited the expression of p16INK4a , at the same time , E2F1 expression were strongly increased in EBV infected cells , however , as for the expression of p 53 and p21WAF1 / CIP1 , there was no difference between EBV infected cells and non infected cells . ^^^ The results show that EBV inactivates p16INK4a / pRB pathway and then induces E2F1 activity and it is implicated that Epstein Barr virus medicated cell cycle deregulation plays an important role in the immortalization of human nasopharyngeal epithelial cells . ^^^ |
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| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| TRIP Br 1 was recently detected by two research groups , which described two separate functions , namely that of a transcriptional integrator of the E2F1 / DP1 / RB cell cycle regulatory pathway ( and then named TRIP Br 1 ) , and that of an antagonist of the cyclin dependent kinase suppression of p16INK4a ( and then named p34SEI 1 ) . ^^^ |
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| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| We previously showed that T oligos act through ATM , p95 / Nbs1 , E2F1 , p16INK4A , p 53 , and the p 53 homologue p 73 to modulate downstream effectors and now additionally demonstrate striking down regulation of the inhibitor of apoptosis protein livin / ML IAP . ^^^ |
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| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| Cdk inhibitors such as p16INK4a and p27Kip1 inhibit pRb phosphorylation by the cyclin D / Cdk4 and cyclin E / Cdk2 complexes , thus keeping E2F1 in an inactive state . ^^^ |
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| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q8N726 and Q01094 |
Pubmed |
SVM Score :0.0 |
| NA |
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