IndraLab

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MDM2 inhibits TP53. 10 / 3877
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"184 Since this early report highlighting the structural bases of the p53/MDM2 interaction, very different classes of MDM2/MDMX (an MDM2 homolog that also inactivates p53) antagonists have been developed as potential anticancer agents, ranging from low-molecular-weight compounds to peptides."
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"However, overexpression of MDM2 can downregulate p53 in cells that should undergo apoptosis, causing aberrant cell cycle progression."
26751476
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"However, upon cellular stress, p53 is phosphorylated resulting in the shutdown of Mdm2 mediated degradation and accumulation of transcriptionally active p53 which activates several targets including cell cycle inhibitors and pro apoptotic proteins resulting in apoptosis or proliferation arrest."
22266868
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"In cellular stress conditions, such as radiation induced DNA damage, the p53 levels are reported to oscillate in a sustained (undamped) way as the p53 suppression by MDM2 is decreased (XREF_FIG) XREF_BIBR."
21829536
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"Phosphorylation of S315 and S376 may induce p53 degradation in endoplasmic reticulum (ER) stressed cells [XREF_BIBR] or MDM2 mediated inhibition of p53 [XREF_BIBR]."
25075982
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"Siva1 binds to Hdm2 and enhances Hdm2 mediated p53 degradation."
19590512
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"Indeed Nutlin-3, a small molecule inhibitor of Mdm2, is able to activate p53, and exhibits antitumor efficacy in cancer cells that express high levels of Mdm2."
23747016
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"As described above, MDM2 and MDMX are two physiological inhibitors of p53 and work together as a complex to independently or together control p53 level and activity in a spatial-temporally specific manner."
28118981
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"It is now widely recognized that RPL5 and RPL11 not incorporated into the 60S ribosome bind preferentially to MDM2, so inhibition of p53 by MDM2 is compromised, causing a stimulation of the p53 pathwa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"MDM2 alterations often result in its overexpression and therefore promote inhibition of p53 activity."
27888811
MDM2 bound to TP53 inhibits TP53. 10 / 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."
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"MDM2 constantly binds to p53, thereby enabling the degradation of p53 by proteasomes [94,95]."
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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]"
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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."
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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."
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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
MDM2 inhibits mutated TP53. 10 / 32
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"Therefore, MDM2 isoforms inhibit MDM2 mediated mutant p53 protein degradation, which in turn promotes mutant p53 accumulation and GOF in tumorigenesis [XREF_BIBR]."
28390900
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"Mutant p53 can be inhibited by mdm2 E3 ligase, although this ligase can not be induced in tumors harboring the mutant p53 that is incompetent as a transcription factor."
27765910
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"Similarly, Ingallina et al. [XREF_BIBR] report that cerivastatin induces MDM2 mediated degradation of several TP53 mutants by inhibiting interaction between mutp53 and HSP90, leading to reduce colony formation of MDA-MB-231 cells [XREF_BIBR]."
30577483
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"In addition to p53 mutations, some tumors inactivate p53 by the amplification of the MDM2 gene (about one third of all sarcomas) (Oliner et al. 1992) or by the localization of p53 in the cell cytoplas[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
9039259
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"Interestingly, Hsp70 is found to partially inhibit Mdm2 mediated degradation of mutant p53."
26734569
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"These results suggest that MDM2 maintains mutant p53 protein levels low in normal tissues, whereas some changes in tumors disrupt MDM2 mediated mutant p53 degradation, thereby leading to mutant p53 protein accumulation in tumors."
28390900
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"MDM2 can promote the degradation of mutant p53, XREF_BIBR, XREF_BIBR although in tumor cells this regulation is disrupted, for example, through the expression of MDM2 isoforms that inhibit full-length MDM2 E3 ligase activity, 51 and mutant p53 protein accumulates."
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"While L11 could inhibit p53 degradation targeted by cotransfected HDM2, L11 expression had no effect on the stability of a p53 mutant that lacks the HDM2 binding site and is not degraded by HDM2 (data[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12842086
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"Over-expression of Mdm2 in either tumor (which do express endogenous functional Mdm2) or in p53 null cells decreased the stability of mutant p53 suggesting that, despite its expression, Mdm2 and JNK are insufficient (amount and affinity) for targeting mutant p53 degradation."
10656807
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"This result is consistent with our previous report that Nutiln, an inhibitor of MDM2 abrogated NSC59984-mediated mutant p53 protein degradation (34)."
34992144
MDM2 bound to MDM4 inhibits TP53. 10 / 13
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"Small molecule RO-5963 blocks homo- and heterodimerization of MDM2 and MDMX, triggering the activation of p53 signalling pathway and the induction of apoptosis (Graves et al., 2012)."
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"This interaction between MDM2 and MDM4 activates the E3 ligase activity of MDM2 and induces proteosomal degradation of p53 to suppress its endogenous cellular levels below the threshold required for transactivation of target genes, such as the cyclin dependent kinase (CDK) inhibitor p21."
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"Therefore, in cancer patients receiving anti-PD1, anti-PDL1, or anti-CTLA4 drugs, regular endocrine assessment is recommended to make early diagnosis and appropriate treatment.This study aimed to elucidate whether p53 reactivation by peptide 3 inhibitor of the MDM2/MDM4 heterodimer (14) formation, whose administration is known to inhibit tumor growth, could have beneficial effects on tumor progression by restoring antitumoral immune responses whilst avoiding the development of autoimmune responses.The effect of p53 reactivator on immunotypes in the peripheral blood of patients affected by thyroid carcinoma was investigated."
34539667
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"Note that in contrast to several studies [41], we did not find Mdm2 stabilization by MdmX and efficient p53 degradation by the Mdm2/MdmX heterodimer."
32075226
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"The examples include MEL23 and its analogs, a number of MMRi (MDM2-MDMX RING domain inhibitors), and a pyrrolidone derivative that inhibits E3 ligase activity of MDM2/MDMX complex to activate p53 (Herman et al., 2011; Zhuang et al., 2012; Wu et al., 2015)."
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"In addition, the interaction between p53 and Mdm2 or MdmX suppresses the transcriptional activities of p53."
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"It has been indicated that MDM2 forms a heterodimer or heterooligomer with MDMX through their C-terminal domains to inhibit p53 during early embryogenesis."
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"MDMX has emerged as a viable target for cancer therapy, both for its own ability to inhibit p53 and its role in the MDM2/MDMX complex, especially in cancers where amplification of MDMX is more prevalent than MDM2 (Gembarska et al., 2012; Burgess et al., 2016)."
35155432
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"In addition, the interaction between p53 and Mdm2 or MdmX suppresses the transcriptional activities of p53 [3]."
20061153
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"An increase in the levels of p53 and phosphorylated p53 could occur as a result of inhibition of the Mdm2-mediated p53 degradation by means of complex formation between Mdm2 and MdmX."
32075226
MDM2-C305F inhibits TP53. 9 / 9
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"Upon induction of the Rps19 deficiency, Mdm2 C305F reversed the p53 response and improved expansion of hematopoietic progenitors in vitro, and ameliorated the anemia in vivo."
25987256
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"23 As a working model, we hypothesized that if the p53 response in Rps19 deficient mice is mediated through the 5S RNP-Mdm2 interaction, the Mdm2 C305F background should reverse the p53 activity and subsequently improve the erythroid phenotype of these mice."
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"Remarkably, a homozygous Mdm2 C305F background reversed the accumulation of p53."
25987256
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"Reduction of the p53 activity in Rps19 deficient hematopoietic stem and progenitor cells by Mdm2 C305F normalized their viability and improved their proliferative capacity, resulting in significantly increased expansion of these cells in vitro."
25987256
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"The Mdm2 C305F mutation, which disrupts the binding of ribosomal proteins L11 and L5 to Mdm2 XREF_BIBR, causes an attenuation of p53 signaling, suggesting that the Mdm2 C305F mutation may alter the progression, rather than initiation, of prostate tumorigenesis in a similar way as p53 heterozygosity."
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"Furthermore, the MDM2 C305F, which is defective in RPL11- and RPL5- binding in vitro and in vivo, has been shown to impair the p53 response to ribosomal stress in animals, strongly demonstrating the essential role of RP-MDM2 interactions in activation of p53 upon ribosomal stress."
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"MDM2 C305F mutation attenuates p53 activation in colon tumors."
27617574
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"Further evidence supporting the adverse effect of high p53 activity in promoting obesity was demonstrated in mutant MDM2 C305F mice that have impaired p53 regulation of lipid metabolism."
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"Mdm2 C305F mutation attenuates p53 response to ribosome biogenesis stress."
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MDM2 bound to CDKN2A inhibits TP53. 8 / 8
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"As mentioned above, ARF interaction with MDM2 causes MDM2 to target MDMX for degradation, and in the event of mitogenic stimulation MDMX is often downregulated to allow p53 activation."
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"In the case of MDM2-p53, it is apparent that both mechanisms are observed under different experimental conditions : induced phosphorylation of p53 can attenuate the p53-MDM2 interaction, and alternatively the human protein p14 ARF can bind to MDM2 and prevent its destruction of p53."
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"Indeed, it has been shown that ARF interacts with MDM2 and prevents MDM2 mediated degradation of p53 [XREF_BIBR]."
20183804
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"When released from nucleoli, Arf binds the central acidic region of MDM2 to inhibit its ubiquitinylation of p53."
25482194
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"The tumour suppressor P19 ARF associates with MDM2 to inhibit the ubiquitination, export and subsequent degradation of p53 [XREF_BIBR, XREF_BIBR]."
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"In vitro, nuclear p14 ARF binds Hdm2 to block Hdm2 dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53."
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"ARF bound Hdm2 blocks Hdm2 dependent nucleocytoplasmic shuttling of p53, to produce nuclear retention and activation of p53 [XREF_BIBR, XREF_BIBR]."
15318938
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"ARF does this by binding to MDM2, a ubiquitin ligase that catalyses p53 degradation; this interaction sequesters MDM2 and also blocks its ligase activity, thereby stabilizing p53."
17439968
MDM2 inhibits TP53. 6 / 6
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"Furthermore, by coimmunoprecipitaton and cotransfection assays, we found that PTEN physically binds p53 in vitro as well as in vivo. Binding of PTEN to p53 attenuated MDM2-mediated p53 inhibition."
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"Upregulation of IGF-1 in myocytes was associated with a protein-to-protein interaction between Mdm2 and p53, which attenuated p53 transcriptional activity for bax, Aogen, and AT1 receptor. Similarly, the amount of Bax, Aogen, and AT1 receptor proteins in these cells decreased"
10205143
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"<p29> mdm2 inhibits p53-mediated transactivation; it inhibits the expression of p53 dependent genes"
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"Upregulation of IGF-1 in myocytes was associated with a protein-to-protein interaction between Mdm2 and p53, which attenuated p53 transcriptional activity for bax, Aogen, and AT1 receptor. Similarly, the amount of Bax, Aogen, and AT1 receptor proteins in these cells decreased"
10205143
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"<p29> mdm2 inhibits p53-mediated transactivation; it inhibits the expression of p53 dependent genes"
10436023
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"Furthermore, by coimmunoprecipitaton and cotransfection assays, we found that PTEN physically binds p53 in vitro as well as in vivo. Binding of PTEN to p53 attenuated MDM2-mediated p53 inhibition."
14559824
Mutated MDM2 inhibits TP53. 5 / 5
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"In agreement with this model, mdm2 mutants defective in p300 but not in p53 binding failed to mediate degradation of p53 and a p53 mutant unable to bind to the N-terminal E6 like domain of p300 was re[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
10214351
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"The mutant MDM2 proteins were unable to inhibit p53 dependent transcription in vivo, which is consistent with prior indications that a physical interaction between the two proteins is required for MDM2 's inhibition of p53."
9131587
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"Importantly, the Deltap1-23A Mdm2 mutant interacts with p53 similarly to wild-type Mdm2 (XREF_SUPPLEMENTARY) and degrades p53 as efficiently as wild-type Mdm2 (XREF_SUPPLEMENTARY)."
20708156
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"In the absence of antagonist, p53 function was reduced ~ 90% by wild-type and mutant HDM2."
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"Thus, it was found that an Mdm2 mutant lacking residues 222-272 also fails to drive p53 degradation, and actually promotes p53 stabilization [88]."
12507556
Modified MDM2 inhibits TP53. 4 / 4
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"Mdm2 is an E3 ubiquitin ligase that targets p53 for mono- and poly-ubiquitination Monoubiquitination mediated by low levels of Mdm2 promotes mitochondrial localization of p53, and elevates nuclear export of p53 to block its transactivational activity; high Mdm2 levels promote polyubiquitination and subsequent proteasome dependent degradation of p53 [XREF_BIBR]."
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"On the other hand, Mdm2 over-expression in cancer cells negatively regulates p53 levels and increased Mdm2 levels would probably abrogate any inhibitory effect of p53 on the CMV promoter activity."
26656605
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"Increased expression of Mdm2 is found to reduce the steady state levels of p53 and decrease the stability of p53 without affecting p53 mRNA levels."
9561848
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"We found that the ectopic expression of MDM2 downregulated the cellular levels of Vif as well as p53 in transfected cells in a dose dependent manner, whereas Parkin and Cul5 did not affect their cellular levels (lanes 2-4 and 5-7, respectively), even though the latter proteins were expressed more than MDM2."
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MDM2-Y489A inhibits TP53. 3 / 4
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"In agreement with previous in vitro studies showing that Mdm2 Y489A does not degrade p53, this data demonstrates that endogenous Mdm2 Y487A has similarly lost this function."
25117711
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"Both Mdm2 Y489A and Mdmx F488A suppresses p53 transactivation function."
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"By normalizing the amount of p21 mRNA to p53 protein, we found that both Mdm2 Y489A and Mdmx F488A reduce p53 specific activity (XREF_SUPPLEMENTARY)."
22266850
Catalytically active MDM2 inhibits TP53. 4 / 4
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"the central module is the interplay between p53 and the Mdm2 protein, which inactivates p53 and targets it for rapid proteolysis."
12485897
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"Akt (PKB) directly phosphorylates multiple protein targets of relevance to apoptosis (Figure 2B), suppressing cell death clearly within the intrinsic pathway (e.g., BAD inactivation, human caspase-9 suppression) and possibly also the extrinsic pathway (e.g., FasL expression) in some types of cells."
12559172
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"The interaction of MDM2 with p53 inhibits p53 transcriptional activity and targets p53 for ubiquitin-dependent degradation. The ability of MDM2 to inhibit p53 functions is antagonized by the ARF oncosuppressor protein."
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"It has been proposed that ARF is expressed only when an E2F signaling threshold is exceeded following oncogenic activation. The main activity of ARF is its ability to bind to p53 inhibitors and to control ribosome biogenesis. Human double minute (HDM2) [mouse double minute 2 (Mdm2) in mouse] and ARF protein binding 1 (BP1)/Mule are two specific E3 ubiquitin ligases that mediate p53 degradation through ubiquitination."
17118707
MDM2 inhibits TP53-R175H. 4 / 4
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"These results indicate that CTM restores mutant p53 R175H function to wt like p53, thus activating the induction of MDM2, which then binds to and negatively regulates p53 R175H."
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"This experiment demonstrated that the absence of CHIP does not impair HSP70 moderated, MDM2 dependent degradation of p53 R175H (XREF_SUPPLEMENTARY)."
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"Ectopic expression of MDM2 clearly down-regulated mutp53 R175H in H1299 cells co-transfected with vectors expressing mutp53 R175H and MDM2 (XREF_FIG), which is consistent with previous reports."
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"Contrary to CHIP mediated degradation, MDM2 dependent degradation of p53 R175H is partially inhibited by HSP70 overexpression (XREF_FIG), while overexpression of dominant negative HSP70 K71S mutant protein stimulates p53 R175H degradation (XREF_FIG)."
23251530
MDM2 bound to RPL11 inhibits TP53. 2 / 2
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"XREF_BIBR Nucleolar stress triggers the nucleoplasmic export of the ribosomal proteins RPL5 and RPL11, which bind MDM2 and block MDM2 mediated p53 degradation, resulting in p53 activation, cell cycle arrest and apoptosis."
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"RPL11, in turn, binds to MDM2, preventing the inactivation of p53."
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MDM2 bound to LATS2 inhibits TP53. 2 / 2
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"Active LATS2 binds and inhibits the E3 ubiquitin ligase MDM2, which targets p53 for destruction, thereby indirectly leading to the stabilization of p53."
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"Active LATS2 also binds to and inhibits the E3 ubiquitin ligase MDM2, which normally targets p53 for destruction."
25126788
MDM2 bound to it inhibits TP53. 2 / 2
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"p19 Arf accumulates in the nucleolus, where it binds NPM1 and Mdm2 to suppress tumor development by inhibiting ribosome biogenesis and initiating p53 dependent senescence and apoptosis, respectively."
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"While exogenous Arf can sequester MDM2 to nucleoli (XREF_FIG), subsequent studies indicate that nucleolar stress releases Arf to the nucleoplasm where it binds and blocks MDM2, XREF_BIBR, XREF_BIBR thus allowing p53 to accumulate and block cell cycle progression (XREF_FIG)."
25482194
MDM2 bound to proteins inhibits TP53. 2 / 2
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"On one hand, these ribosomal proteins bind MDM2 and inhibit the E3 ubiquitin ligase activity resulting in stabilization of p53."
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"The released ribosomal proteins bind to MDM2 to block its ubiquitinylation of p53, leading to p53 stabilization and subsequent induction of p53 mediated G 1 cell cycle arrest or apoptosis."
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MDM2 inhibits unphosphorylated TP53. 1 / 1
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"The dephosphorylated p53 can then be degraded by MDM2 induced mechanisms, resulting in nicotine induced cell survival and tumorigenesis."
27769050
MDM2-C462A inhibits TP53. 1 / 1
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"Here, we show in vivo that the Mdm2 (C462A) protein not only fails to suppress p53, but compared to the complete absence of Mdm2, Mdm2 (C462A) actually enhances p53 transcriptional activity toward p53 target genes p21 and CDKN1A, MDM2, BAX, NOXA, and 14-3-3sigma."
22666487
MDM2 bound to NOP16 inhibits TP53. 1 / 1
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"In the cytoplasm, HSPC111 might directly interact with and stabilize MDM2, which could promote P53 degradation via ubiquitination and subsequently accelerate tumor progression [XREF_BIBR]."
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MDM2 bound to PTK2 inhibits TP53. 1 / 1
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"Recently, the direct interaction of the N-terminal FERM domain of FAK and p53 proteins has been shown and also FAK interaction with Mdm-2 protein has been demonstrated to down-regulate p53 [XREF_BIBR]."
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MDM2-R175H inhibits TP53. 1 / 1
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"Thus, inhibition of RhoA activity through inhibition of the mevalonate-RhoA axis by an HMG-CoA-R inhibitor (cerivastatin) or an inhibitor of geranylgeranyltransferase type I (GGTI-298) reduces HDAC6 activity and hence induces hyperacetylation of HSP90, leading to dissociation of mutp53 from HSP90 and degradation of mutp53 by MDM2 (R175H, L194F, M237I, R249S, R273H)."
30577483
MDM2 bound to POL2A inhibits TP53. 1 / 1
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"Interestingly, in mammals, a link exists between the regulation of Pol epsilon activity and p53, the functional homologue of SOG1 : MDM2 (Mouse Double Minute 2) can bind the C-terminus of Pol2A and is thought to simultaneously modulate Pol epsilon functions in response to stress and control cell cycle progression by regulating p53 degradation, similar mechanisms might be conserved in plants to maintain genome integrity."
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MDM2 bound to RB1 inhibits TP53. 1 / 1
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"Rb directly binds to MDM2 to antagonize these functions and then inhibits p53 activity."
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MDM2 inhibits acetylated TP53. 1 / 1
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"Furthermore, while p53 is strongly stabilized and highly acetylated in stressed cells, acetylation of the C-terminal multiple lysine sites may occupy the same sites responsible for Mdm2 mediated ubiqu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
11672522
MDM2 bound to NUMB inhibits TP53. 1 / 1
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"Interestingly, NUMB, a suppressor of NOTCH, forms a tri-complex with TP53 and its ubiquitin ligase HDM2 to prevent ubiquitination and consequent TP53 degradation."
30087852
MDM2 inhibits TP53-Y107G. 1 / 1
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"Interestingly, the three unfolded mutants p53 Y107G, p53-T155D, and p53-L265A were still degraded by MDM2."
22046250
MDM2-M237I inhibits TP53. 1 / 1
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"Thus, inhibition of RhoA activity through inhibition of the mevalonate-RhoA axis by an HMG-CoA-R inhibitor (cerivastatin) or an inhibitor of geranylgeranyltransferase type I (GGTI-298) reduces HDAC6 activity and hence induces hyperacetylation of HSP90, leading to dissociation of mutp53 from HSP90 and degradation of mutp53 by MDM2 (R175H, L194F, M237I, R249S, R273H)."
30577483
MDM2 bound to MYL6B inhibits TP53. 1 / 1
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"But, in this study we found that MYL6B could bind both MDM2 and p53 protein, accelerate the p53 degradation and promote HCC development."
29439719
MDM2 bound to EBNA-LP inhibits TP53. 1 / 1
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"The binding of EBNA-5 to MDM2 also could impair the functional activity of p53."
20473904
MDM2 bound to PSMD10 inhibits TP53. 1 / 1
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"The studies of gankyrin dependent promotion of liver cancer have indicated that gankyrin could not only bind to mdm2 and enhance degradation of p53 but also interact with Rb to reduce its stability."
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MDM2 bound to S100A9 inhibits TP53. 1 / 1
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"13 p14 arf lies upstream of p53 and binds the p53 inhibitor HDM2 in order to activate p53."
20038820
MDM2 bound to TRIM28 inhibits TP53. 1 / 1
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"TRIM28 through its coiled-coil domain binds to MDM2 and promotes p53 degradation."
29479529
MDM2 bound to MDM4 and TP53 inhibits TP53. 1 / 1
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"In the present study, however, we have uncovered a novel mechanism of p53 inactivation for inducing cisplatin resistance whereby the heterozygous V172F missense mutation in p53 enhances MDM4 recruitment into the p53, MDM2, and MDM4 complex that prevents p53 dependent transcriptional activity and apoptosis."
26876197
MDM2 bound to region inhibits TP53. 1 / 1
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"Mdm2 binds to the N-terminal region and represses p53 activity via two mechanisms : by promoting degradation and blocking p53 transcriptional activation [8-10]."
15865933
MDM2 bound to NPM1 inhibits TP53. 1 / 1
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"Kurki et al 11 reported that interaction between MDM2 (a negative regulator of p53) and nucleoplasmic NPM, translocated from nucleoli due to cellular stress, led to stabilization and possibly also act[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21689627
MDM2 bound to E3_Ub_ligase inhibits TP53. 1 / 1
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"Mdm2, an E3 ubiquitin ligase, binds and induces p53 degradation, exhibiting oncogenic activity as a negative regulator of the p53 tumor suppressor [2]."
36171205
MDM2-R249S inhibits TP53. 1 / 1
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"Thus, inhibition of RhoA activity through inhibition of the mevalonate-RhoA axis by an HMG-CoA-R inhibitor (cerivastatin) or an inhibitor of geranylgeranyltransferase type I (GGTI-298) reduces HDAC6 activity and hence induces hyperacetylation of HSP90, leading to dissociation of mutp53 from HSP90 and degradation of mutp53 by MDM2 (R175H, L194F, M237I, R249S, R273H)."
30577483
MDM2-Y487A inhibits TP53. 1 / 1
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"Endogenous Mdm2 Y487A Does Not Degrade p53 but Maintains Normal Binding Dynamics."
25117711
MDM2-L194F inhibits TP53. 1 / 1
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"Thus, inhibition of RhoA activity through inhibition of the mevalonate-RhoA axis by an HMG-CoA-R inhibitor (cerivastatin) or an inhibitor of geranylgeranyltransferase type I (GGTI-298) reduces HDAC6 activity and hence induces hyperacetylation of HSP90, leading to dissociation of mutp53 from HSP90 and degradation of mutp53 by MDM2 (R175H, L194F, M237I, R249S, R273H)."
30577483
MDM2-R273H inhibits TP53. 1 / 1
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"Thus, inhibition of RhoA activity through inhibition of the mevalonate-RhoA axis by an HMG-CoA-R inhibitor (cerivastatin) or an inhibitor of geranylgeranyltransferase type I (GGTI-298) reduces HDAC6 activity and hence induces hyperacetylation of HSP90, leading to dissociation of mutp53 from HSP90 and degradation of mutp53 by MDM2 (R175H, L194F, M237I, R249S, R273H)."
30577483
MDM2-C464A inhibits TP53. 1 / 1
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"Consistently, when Axin was immunoprecipitated, both HIPK2 and p53 in the precipitates were simultaneously reduced by co-expression of MDM2 or its mutant MDM2 (C464A) (XREF_FIG)."
23826318
MDM2 bound to RPL5 inhibits TP53. 1 / 1
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"XREF_BIBR Nucleolar stress triggers the nucleoplasmic export of the ribosomal proteins RPL5 and RPL11, which bind MDM2 and block MDM2 mediated p53 degradation, resulting in p53 activation, cell cycle arrest and apoptosis."
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MDM2 bound to EP300 inhibits TP53. 1 / 1
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"To test the hypothesis that MDM2 and p300 complexes promote p53 degradation, the MDM2 and p300 binding process was subjected to genetic analysis."
9809062
MDM2 bound to STAT5 inhibits TP53. 1 / 1
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"Therefore, we have discovered a surprising role and its related mechanism for MDM2 in stabilizing STAT5 in T cells.Given that MDM2 interacts with p53 and mediates p53 degradation in tumor cells , we have demonstrated that MDM2 can regulate T survival and function in the absence of p53."
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MDM2 inhibits TP53-R158G. 1 / 1
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"H2170 LUSC cells that are homozygous for p53 R158G demonstrated impaired MDM2 and CDKN1A transactivation when treated with Nutlin-3a, a MDM2 antagonist, as compared to MRC5 (p53 wt) cells, indicating loss of p53 function."
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Phosphorylated MDM2 inhibits TP53. 1 / 1
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"The phosphorylated MDM2 enhances p53 degradation 15; in addition, blocking MDM2 binding to p53 with a small molecule nutlin-3 protects rabbits from retinal detachment in a PVR rabbit model."
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