IndraLab

Statements

MDM2 bound to TP53 inhibits TP53. 71 / 71
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"MDM2 binds to p53, enhancing the degradation of p53 through the ubiquitination pathway 57-60, as well as concealing the activation domain of p53 (Ref."
10462750
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"Both DNA-PKcs and ATM can phosphorylate p53 at serine 15, which inhibits the MDM2 binding to p53 and promotes both nuclear accumulation and activation of p53 in response to DNA damage."
22726545
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"MDM2 constantly binds to p53, thereby enabling the degradation of p53 by proteasomes [94,95]."
32498447
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"Three amino acids of p53 (Phelg, Trp23 and Leu26) are buried deep into the Mdm2 pocke09,2 Interaction between Mdm2 and p53 has previously been shown to block the bio- logical activity of p53, presumab[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
9357310
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"Binding of MDM2 to p53 inhibits the transcriptional activity of p53 and targets it for proteasomal degradation [XREF_BIBR]."
23351152
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"In addition, binding of Mdm2 to p53 can directly inhibit the transcriptional activity of p53 through a number of mechanisms."
24121268
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"A homolog of Mdm2, MdmX (or Mdm4), can similarly bind p53 and inhibit p53 dependent transactivation although unlike Mdm2 it lacks E3 ubiquitin ligase activity [XREF_BIBR]."
25545885
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"Nutlin-3, a specific inhibitor of the MDM2 and p53 interaction, is able to relieve the ensuing p53 attenuation, which leads to cell cycle arrest and enhanced apoptosis in the affected cells."
24240203
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"circFoxo3 binds to MDM2, which is associated with p53, to induce p53 degradation."
29403493
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"HDM2 oncoprotein physically associated with p53 and inhibits wild-type p53 transactivation function."
15921850
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"MDM2 interacts with p53, inducing its inactivation by blocking the arrest of p53 in cell cycle stage G1, thereby promoting the cell cycle."
24348821
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"These data build a compelling case in favor of MDM2 as the mediator of p53 degradation.Mere complex formation between MDM2 and p53 is not sufficient to mediate p53 degradation."
10721693
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"The similarity between the ZCP-MDM2 interaction and the P53-MDM2 interaction suggests that ZCP blocks the formation of the MDM2 and P53 complex, causing P53 release."
28775961
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"For example, MDM2 can directly bind to p53 to inhibit its transcriptional activity; quickly enhance the ubiquitination and degradation of p53 through ubiquitin-E3 ligase; and promote p53 degradation by blocking p53 's transport from the nucleus to the cytoplasm XREF_BIBR XREF_BIBR."
28045062
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"MDM2 directly binds to and forms a complex with p53, inhibiting the transactivation of p53."
32968059
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"MDM2 binds and blocks the N-terminal trans -activation domain of p53, causing the accumulation of p53 in these cells before ubiquitination."
26520377
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"In the basal setting, Mdm2 binds p53 and promotes p53 degradation."
22264782
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"Ribavirin stimulated the expression of the p53 dependent gene Mdm2, which can bind to p53 and inhibit the activation of p53 by targeting p53 protein for degradation through the ubiquitin dependent proteolytic pathway XREF_BIBR."
22962590
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"However, in response to cellular stress (eg, DNA damage, hypoxia, oncogenic activation), the interaction between MDM2 and P53 is disrupted, which leads to stabilization of P53."
31991614
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"Mdm2, an important negative regulator of the p53 tumor suppressor, binds to p53 and inhibits p53 mediated transactivation."
23202902
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"In this process, MDM2 binds directly to p53 and mediates the ubiquitination dependent degradation of p53."
29584707
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"MDM2 can bind directly to p53 and promote the degradation of p53 protein (Momand et al., 1992; Oliner et al., 1992); this mechanism forms a circuit for negative regulation of p53."
11511362
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"Our findings are in agreement with a report showing that CMA degrades mutant p53 in a lysosome dependent manner.17 We showed that inhibition of p53 and Mdm2 interaction using nutlin-3 or silencing Mdm2 did not prevent degradation of p53 in an HCV infected culture."
29404458
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"MDM2 binding to p53 inhibits p53 dependent apoptosis by suppressing transcriptional activation of p53 in response to DNA damage, exporting p53 out of the nuclease and targeting p53 for proteasomal degradation due to E3 ligase activity of MDM2."
21105689
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"The first small-molecule inhibitor of p53 and mDM2 interaction, 4, 5-dihydroimidazoline (nutlin, Roche), was demonstrated to bind to mDM2 and induce p53 dependent cell cycle arrest at low micromolar levels in vitro [XREF_BIBR]."
26883110
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"Very recently, we identified that p48 Ebp1 physically associates with HDM2 and enhances the interaction between HDM2 and p53, promoting p53 degradation in human glioma cells with poor clinical outcome[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21930127
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"Small-molecule MDM2 antagonists that disrupt the interaction between p53 and MDM2 to activate the p53 pathway have shown initial signs of antitumor efficacy in patients with solid and hematologic malignancies."
28425916
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"Therefore, the disruption of the MDM2 and p53 complex by small molecules such as nutlin-3a and the administration of the active p53 protein can effectively restore the apoptotic activity of the p53 protein in tumor cells."
32264215
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"By dephosphorylation of MDM2 and making its stability, Wip1 can enhance the interaction between MDM2 and p53, to promote the degradation of p53 protein [XREF_BIBR - XREF_BIBR]."
28903382
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"The direct binding of Mdm2 to p53 inhibits the transcriptional activation function of p53 [XREF_BIBR]."
22575647
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"MDM2 may bind P53 and promote P53 degradation at baseline but stimulate P53 translation under stress XREF_BIBR."
22844496
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"MDM2 binds p53 directly through N-terminal transactivation domain to inhibit p53 transactivation."
32477121
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"In addition, HDM2 binding to p53 blocks its transactivation domain preventing p53 transcriptional activation of its target genes."
25965177
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"It was known prior to these reports that MDM2 could bind p53 and prevent p53 dependent transcriptional activation of target genes, that tumor cells that had elevated MDM2 also contained wild-type p53 [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
8939636
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"Surprisingly, the protein product of mdm2 binds p53 and inhibits p53 mediated transcriptional activation (Momand et al., 1992; Oliner et al., 1993; Zauberman et al., 1993)."
8898354
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"Interestingly, the binding between MDM2 and p53 can negatively regulate the transrepression function of p53 (Chen et al. 1995)."
10078201
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"XREF_BIBR, XREF_BIBR As proteasomal degradation is not compromised in E/R positive leukemic cell lines (data not shown), we tested whether Nutlin-3, a small molecule that disrupts the MDM2 and p53 interaction, can reactivate p53 signaling."
24240203
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"Mdm2 binds to p53 in a region of its transactivation domain and blocks the ability of p53 to activate transcription (reviewed in [106,107])."
10967423
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"Experimental inhibition of HDM2 and p53 interactions restored p53 activity, and decreased survival of infected cells."
25605238
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"For this reason, inhibition of the interaction between MDM2 and p53 to reactivate endogenous p53 activity offers the opportunity for therapeutic intervention, particularly in GBMs."
23977270
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"XREF_BIBR, XREF_BIBR, XREF_BIBR Except for cancer selected p53 mutations, the p53 activity is mainly inhibited by p53 binding proteins Mdm2 and MdmX ((MDM4), mouse double minute 4) in normal and cancer cells."
26720344
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"UBX0101 is an inhibitor of the interaction between MDM2 and p53 which allows p53 to facilitate the induction of apoptosis [12,39]."
35447516
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"Nutlin-3, a small molecule MDM2 antagonist blocking interaction between MDM2 and p53, activates p53 resulting in cell growth arrest or apoptosis in various cancer cells."
19648117
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"EZH2 was verified to bind to MDM2, and MDM2 could bind p53 to promote p53 degradation, which then influenced CRC progression [33, 34]."
33879635
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"It is reported that MDM2 can bind to p53 and block the p53 signaling pathway, and could also promote the degradation of p53; when p53 is activated, in turn, it also inhibits the transcriptional expression of MDM2."
33425912
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"MDM2 binds directly to p53 and represses its transcriptional activity, promoting p53 degradation."
37326394
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"The binding of MDM2 to p53 inactivates p53 and removes growth regulation by this protein, in a manner similar to that seen in virally induced cancers6,8."
8048160
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"Acting as an ubiquitin (Ub) protein ligase (E3), MDM2 (also called HDM2) can bind and ubiquitinate TP53 and promote rapid degradation of TP53 through the ubiquitin proteolysis pathway, which keeps TP53 at low levels in the absence of stress signals."
24667108
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"Inhibition of p53 and Mdm2 interactions by small molecule (nutlin-3) or silencing Mdm2 did not rescue the p53 degradation, indicating that HCV infection induces degradation of p53 independent of the Mdm2 pathway."
29404458
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"It is well established that p53-MDM2 forms a negative auto-regulatory feedback loop in which p53 transactivates MDM2, whereas induced MDM2 binds to p53 and promotes p53 degradation."
21170087
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"First, Mdm2 binds p53 19 and inhibits the transactivation function of p53 20,21."
11718560
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"Disruption of the MDM2 and p53 interaction leads to increased p53 levels and restored p53 transcriptional activity, indicating restoration of the genome integrity check and therapeutic potential for MDM2 and p53 binding antagonists."
11148027
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"Under non-stressed conditions, MDM2 binds specifically to p53 and promotes the ubiquitination and proteasomal degradation of p53, which maintains p53 at low levels."
34869377
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"The interaction between Mdm2 and p53 directly inhibits p53 transcription activity and blocks p53 dependent activation of downstream effectors [5]."
24755078
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"RITA was shown to disrupt the interaction between p53 and MDM2, and was able to reactivate p53 in tumours that have aberrant MDM2 expression."
17211478
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"RITA is known to disrupt the p53 and MDM2 complex and hereby reduces degradation of wild-type p53 and reactivates its transcriptional function XREF_BIBR, XREF_BIBR."
28284059
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"Pharmacological targeting of the pivotal Mdm2 and p53 interaction with natural compounds, small molecules, and even stapled (helix linked) peptides, has been extensively investigated in an effort to restore the tumor suppressor activity of wild-type p53."
30101008
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"Inhibition of MDM2 binding to p53 prevents its degradation and activates p53 to function in the cell."
30498096
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"Elevated Mdm2 protein levels induced by Ras activation may bind those mutated forms of p53 and abolish remaining p53 function."
11057904
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"Small molecule inhibitors of the MDM2 and p53 interaction have been identified, such as the Nutlins XREF_BIBR, which were the first generation of agents directly targeting this pathway, and bind in MDM2 's p53 binding pocket in the N-terminal region to induce p53 accumulation."
25181509
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"Phosphorylation of p53 at serine 15 attenuates MDM2 binding to p53 and thus promotes p53 stability 55."
28842590
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"P53 activates the transcription of Mdm2, which binds p53 (40), ubiquitinates it, and thus initiates the proteasomal degradation of p53 both in the nucleus and cytosol (41)."
20197027
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"We assume in these patients that MDM2 formed a complex with wild-type TP53 and inhibited the ability of TP53 to activate transcription of its target gene (s)."
28258440
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"Small molecule inhibitors of the interaction between HDM-2 and p53 such as nutlin restore p53 function in tumor cells with wtp53."
18765533
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"The interaction between Mdm2 and p53 is essential for Mdm2 to block the p53 response."
11927286
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"MDM2 binds to p53, and promotes degradation of p53 through ubiquitin-proteasome degradation."
21504625
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"In unstressed cells, p53 activity is negatively regulated by MDM2 (Mouse Double Minute 2), which binds to p53 and promotes its proteasomal degradation [5,6,7,8]."
31835684
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"MDM2 binds to p53, inactivates p53 transcription function, inhibits p53 acetylation, and promotes p53 degradation."
16107876
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"In turn, MDM2 binds to p53, which (a) blocks its N-terminal transactivation domain and (b) targets p53 for degradation via the ubiquitin-proteasome system following ubiquitinylation through its E3 ligase activity."
15452548
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"102 In cells containing wild-type p53 and subjected to various stimuli, p53 normally transcribes the MDM2 gene to produce MDM2 protein, and in turn, the binding of MDM2 to p53 directly inhibits p53 function.102 Notably, MDM2 expression is abnormally upregulated in different cancer types."
36134387
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"Embryonic lethality of Mdm2 C462A mice is rescued by p53 loss indicating that Mdm2 binding to p53 is not sufficient to inhibit p53 in vivo."
21726810