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phosphosite cbn pc11 biopax bel_lc signor biogrid tas lincs_drug hprd trrust | geneways tees isi trips rlimsp medscan sparser reach
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TP53 affects MDM2
2 474 21 | 50 6005 2773
2 474 12 | 50 4963 2671
biogrid
No evidence text available
reach
"For tumors that retain wild-type p53, therapeutic strategies aimed at removing the inhibitory activity of MDM2 on p53 are under development and to date have focused on drugs that prevent the binding of p53 to MDM2."
sparser
"In our recent paper we report that p53 reactivation by a small molecule inhibitor of p53-MDM2 interaction, Nutlin-3a, induces selective and massive apoptosis in PEL cells, and has striking anti-tumor activity in a mouse xenograft PEL model."
sparser
"A number of small molecules and peptides have been identified that impair the interaction of p53 with mdm2, an important negative regulator of p53 stability xref ."
biogrid
No evidence text available
sparser
"Additionally, the interaction between MDM2 and p53 blocks the binding of p53 to targeted DNAs and transports p53 from the nucleus to the cytoplasm, rendering p53 ineffective as a transcriptional factor."
sparser
"However, unlike its setting in regulating MDM2p53 interaction ( xref ), S7 did not interrupt the MDM2–GADD45α association in vivo ( xref F)."
reach
"Nutlin-3a inhibits the interaction between MDM2 and p53, which stabilizes p53 and then selectively induces senescence in cancer cells."
sparser
"While on the one hand MDM2 binds to p53 and blocks its N-terminal transactivation domain, it induces p53's degradation via ubiquitin-proteasome machinery on the other hand [ xref ]."
sparser
"Extensive investigations have demonstrated that MDM2 protein–protein interactions with p53 and other p53 family members (p63 and p73) block their ability to function as transcription factors that regulate cell growth and survival."
| 216 8
sparser
"MdmX interacts with p53 or Mdm2 to form transcriptionally inactive p53MdmX or enzymatically inactive Mdm2MdmX."
sparser
"Nutlin binds to MDM2 versus MDMX with a 40-fold stronger inhibition constant ( K i of 0.7 versus 28  μ M), whereas MDMX and MDM2 bind to p53 with similar affinities ( K d =0.5  μ M). xref , xref Thus, in the presence of Nutlin, MDMX is still able to bind to p53 and repress its transcriptional activity. xref , xref Consequently, knockdown of MDMX was reported to potentiate Nutlin-induced apoptosis. xref , xref , xref We confirmed these findings."
sparser
"The interactions of p53 with Mdm2 and Mdmx, mediated via the TA domain of p53 have been well-documented ( xref ; xref ; xref ; xref )."
sparser
"We added 10% fetal bovine serum (FBS) into the lysate BiLC assays to determine directly whether serum reduces the ability of stapled peptides to disrupt p53-Mdm2 and p53-Mdm4 interactions."
sparser
"An alternative independent strategy for mitochondria-targeted radiation mitigation was tested using a small molecule inhibitor of p53 binding to mdm2 and mdm4 ( xref – xref ), with the goal to enhance the bioavailability of p53 and enhance cellular repair processes ( xref , xref )."
sparser
"This perhaps suggests that either MDM2p53 or MDMXp53 binding is not sufficient for complete p53 activity suppression, or that without E3 ligase-mediated degradation by MDM2, increased levels of p53 are also spontaneously more active."
sparser
"Our ongoing interest in the rational design of small molecule antagonists of the p53 Mdm2 and Mdm4 interactions has prompted us to design scaffolds with novel tryptophan mimicking features. xref While Wang et al. introduced the oxindole anchor, we introduced indole and others are using p-substituted phenyl groups, we wanted to explore here the benzimidazolidinone moiety as a tryptophan mimicking moiety. xref For reasons of resources we restricted our search of suitable benzimidazolidinone scaffolds to multicomponent reactions as opposed to sequential multi step syntheses."
sparser
"In particular, studies inhibiting the interaction of p53 with its negative regulators MDMX and MDM2 are an important field in drug discovery."
sparser
"Triarylpyrroles e.g. 4c and 4s inhibit the MDM2p53 and MDMXp53 protein–protein interactions."
sparser
"The association of p53 with MDM2 and MDM4 is disrupted with phosphorylation by various enzymes such as DNA-PK, ABL, ATR, ATM and CHK -all activated by genotoxic stressors [ xref ]."
TP53 binds USP7 and MDM2. 10 / 37
| 26 11
reach
"Collectively, these results suggest that nucleolin is involved in the formation of the HAUSP, Mdm2, and p53 complex, and the HAUSP-nucleolin interaction requires the presence of Mdm2 in normal condition."
sparser
"Crystal structure analysis visualized HAUSP-p53 and HAUSP-Mdm2 interactions via HAUSP binding motif P/AXXS xref ."
sparser
"As USP7 binds both p53 and Mdm2 with the same N-terminal domain [ xref ], the overall effect of its enzymatic activity is highly dependent on the relative affinity for the two targets."
sparser
"The accumulated evidence regarding the interactions of USP7 and MDM2 with p53 indicates that these interactions are important in regulating the stability of p53 under both physiological and pathological conditions."
sparser
"Moreover, p53 was found to be upregulated in MDM2 −/− p53 −/− double-deficient MEFs after co-transfection of both p53 and ABRO1, indicating that ABRO1-dependent p53 stabilization is made possible by enhanced p53-USP7 interaction without effects on p53-MDM2 interaction and MDM2 stability."
sparser
"In addition, USP7 can interact indirectly with p53, using Mdm2 as a bridge, resulting in the formation of USP7-Mdm2-p53 complexes."
reach
"The HAUSP, p53, and Mdm2 complex and p53-nucleolin interplay in DNA damage have been identified XREF_BIBR XREF_BIBR XREF_BIBR; however, the molecular relation between these two findings was poorly understood."
sparser
"The interactions between HAUSP and p53 or MDM2 are likely to be more complex in vivo, not only due to the presence of multiple binding sites in MDM2 but also because of the oligomeric nature of p53 and possibly HAUSP."
sparser
"Because WDR79 affected the interaction of USP7 with Mdm2 and p53, we hypothesized that WDR79 is involved in USP7-mediated regulation of Mdm2 and p53."
reach
"The authors find that genotoxic stress induces a shift in complex formation from a p53, MDM2, and USP7 complex to p53/GMPS/USP7."
| 23 2
sparser
"One possible reason might be that p14ARF could bind to HDM2 in both nucleolus and nucleoplasm, xref , xref so that the SOX6-induced translocation of p14ARF could increase the formation of p14ARF-HDM2-p53 ternary complex but not affect the ability of p14ARF to bind with HDM2."
sparser
"Association of p14 ARF , p53 and Hdm2 with clinicopathological factors."
sparser
"It binds to p14ARF-hMDM2-p53 complexes."
sparser
"In the order hand, p14 ARF   interacts with MDM2 and blocks MDM2 to target p53 to degradation, contributing with p53 stabilization."
sparser
"Interestingly, Plk1 is involved in many regulatory feedback loops that are associated with p53, MDM2 and p16 INK4A /p14 ARF (reviewed in depth in [ xref ]) and with up to 84% of human melanomas expressing wild-type p53, the reactivation of p53 signaling would provide a distinct advantage in the remediation of melanomas with diverse mutational backgrounds [ xref ]."
sparser
"Previous studies have revealed that the p14 alternate reading frame tumor suppressor (p14ARF) is capable of inhibiting the nuclear export and p53-ubiquitination activity of HDM2, as well as increasing the stability of the p53 protein by forming the p14ARF-HDM2-p53 ternary complex. xref , xref , xref To test whether SOX6 can promote formation of the p14ARF-HDM2-p53 complex, HeLa SOX6-tet cells were co-transfected with pLex-p14ARF-myc and pLex-HDM2-V5 plasmids, and the cell lysates were subjected to co-immunoprecipitation assay."
sparser
"It has been shown to bind to multiple proteins, p14 ARF , p53 and HDM2 of ARF-p53-p21 tumor suppressor axis, and control cancer cell proliferation in two directions in a dose dependent way xref xref xref ."
sparser
"In vitro , nuclear p14 ARF binds Hdm2 to block Hdm2-dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53."
sparser
"The nucleoplasmic p14ARF promotes formation of the p14ARF-p53-HDM2 ternary complex and inhibits the nuclear export and p53-ubiquitination activity of HDM2, thereby stabilizing and activating p53."
sparser
"In addition, MDM2 and p14 ARF not only interact with p53 but also interact with other important cellular proteins, including Rb, ATM, and E2F/DP1, to exert their oncogenic and tumor suppressor function, respectively xref , xref ."
| 19 3
sparser
"We next investigated if inhibition of lincRNA-p21, which affected interactions between p300, MDM2, and p53 proteins without altering p53 protein level, influenced p53 binding to the promoters/enhancers of its target genes."
sparser
"In fact, single mutation of Ser15 or Ser20 to alanine on full-length p53 has been shown to affect p53-dependent processes in transcription and apoptotic assays, p53-protein stability assays, and in th[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"Moreover, most of the endogenous MDM2 is bound to p300, and genetic analysis implies that specific interactions of p53 and MDM2 with p300 C/H1 are important steps in the MDM2-directed turnover of p53."
sparser
"In anoxia, p53 competitively binds to p300 and Mdm2 targets HIF-1α for degradation; thus, the HIF-1α ac level drops markedly, and rather low levels of p21 are induced."
sparser
"It is likely that, similar to p53-MDM2 and p53-p300 interactions, the p53-KLF4 interaction is also affected by these mutations, contributing to the loss of transactivation of cell-cycle arrest genes."
sparser
"These observations suggest that lincRNA-p21, a transcriptional target of p53, can feed back and regulate the activity of p53, at least in part, by modulating the interaction of p53, p300 and MDM2."
reach
"To understand how the lincRNA-p21 and MDM2 interaction affects the formation of the p53, p300, and MDM2 complex, co-immunoprecipitation (Co-IP) experiments were performed."
sparser
"Mutated TP53 residues 18 and 27 interact with both MDM2 and EP300 ( xref )."
sparser
"First, the work of Grossman and colleagues suggested that degradation of p53 by HDM2 is linked to the formation of a multimeric complex containing p53, p300, and HDM2 [55] ."
reach
"However, the binding of p53 with TAg also increases the half-life and steady-state levels of p53 in cell culture partly due to the entrapment of the p300, mdm2, and p53 complex that targets p53 for degradation."
| 20 1
sparser
"In the nucleus, ARF interacts physically and functionally with Mdm2 to inhibit cell cycle progression through activation of p53."
sparser
"Because ARF binding does not compromise the ability of Mdm2 to interact with p53, both binary ARFMdm2 and ternary ARFMdm2p53 complexes can be formed, and their roles in vivo remain a subject of s[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"It now appears that p19 ARF binds MDM2 to prevent the degradation of p53 and thus permits p53-induced apoptosis or growth arrest (see Figure 1b ) [31 •• ,32 •• ,33 • ,34 • ] ."
sparser
"It should be emphasized, however, that overexpression of Mdm2 in some tumors lacking ARF points to more complex biochemical interactions between ARF, Mdm2, and p53 than had been previously expected."
sparser
"Another model proposes that ARF forms a ternary complex with MDM2 and p53 in the nucleoplasm, thereby blocking p53 nuclear export and stabilizing and activating p53 ."
sparser
"ARF-promoted MDM2 degradation is associated with MDM2 modification and concurrent p53 stabilization and accumulation."
sparser
"Intriguingly, ARF, MDM2, and p53 can form a stable ternary complex, likely bridged by MDM2 via its two separate domains, which can independently interact with p53 and ARF ( Figure 3 )."
sparser
"Complicated feedback and control mechanisms regulate ARF, Mdm2, and p53 interactions."
sparser
"However, this does not appear to be the case [87,94] , consistent with another similar scenario, such as the protection of p53 by ARF [99] , where Mdm2, p53, and ARF form a complex in which p53 is a[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
reach
"SUMO-1 conjugation is effected via the coordinated collaboration of Mdm2 and the tumour-suppressor ARF, which are both required in a p53, Mdm2, and ARF complex to stimulate p53 SUMOylation via SUMOylation and nucleolar targeting of Mdm2."
sparser
"For instance, Numb is an important p53 regulator by forming a tripartite complex with tumor suppressor p53 and its E3 ligase, Mdm2, thus inhibiting the degradation of p53 and promoting its tumor suppressive functions. xref Many other functions of Numb, such as muscle stem cell proliferation and regeneration, xref endocytosis and ubiquitination, have also been reported. xref Recently, it was shown that post-translational modifications, including phosphorylation and methylation, can affect Numb functions like asymmetric distribution as well as tumor suppressive roles based on its regulation on p53. xref – xref p53, a well-studied transcription factor, is crucial for mediating cell cycle arrest and apoptosis in response to DNA damage. xref Further, it has been documented that disruption of the p53 pathway has always been associated with therapeutic resistance and poor clinical outcomes. xref Of note, cancer cells without Numb are less sensitive to chemotherapeutic drugs than cells expressing a functional Numb. xref Thus, understanding how Numb is regulated will provide us novel opportunities for improving the efficacy of existing chemotherapy."
sparser
"For detailed information on the interactions of MDM2 and other E3 ligases with the p53 family members, see the reviews [ xref , xref , xref , xref , xref , xref , xref , xref , xref ]."
sparser
"To this regard, before p53 induction, a disruption between the complex formed by p53 and MDM2, a p53-specific E3 ubiquitin ligase, is needed for its biological response [19] ."
sparser
"A similar strategy has been successfully applied to the selective cancer cell blockade of interactions between mdm2 ubiquitin ligase and p53 using nutlins [ xref ]."
sparser
"The interaction between p53 and E3 ligases such as MDM2, all transcription targets of p53, leads to the ubiquitination and rapid degradation of p53."
sparser
"Epstein Barr virus (EBV) nuclear antigen 3C (EBNA3C) forms a trimeric complex with p53 and Mdm2, which enhances the ubiquitin ligase activity of Mdm2 for p53."
sparser
"In the absence of cellular stress, p53 is bound by its negative regulator, Mdm2, an E3 ubiquitin ligase that promotes its degradation."
sparser
"Some of these modifications are known to influence the interaction between p53 and the E3 ubiquitin ligase, MDM2, which is a major mechanism for controlling p53 through inducing proteasomal degradation."
sparser
"This modification impairs the interaction between p53 and MDM2, the main negative regulatory E3 ubiquitin ligase of p53, to relieve both ubiquitin-dependent and ubiquitin-independent repression mediated by MDM2 from p53 xref , xref ."
sparser
"We note that the p53–COP1 interaction is characterized by a higher affinity and by a longer lifetime with respect to the complex formed by p53 and its major ubiquitin ligase, MDM2, strengthening the importance of COP1 in p53 downregulation."
TP53 binds MDM2 and MDM2. 10 / 19
| 19
sparser
"Inhibiting p53 binding to both Hdm2 and HdmX should be a promising clinical approach to reactivate p53 in the cancer setting, but previous studies have suggested that the discovery of dual Hdm2/HdmX inhibitors will be difficult."
sparser
"It interacts with p53, Hdm2 and Hdmx, and its deubiquitinating function towards these proteins protects cells from apoptosis [ xref , xref ]."
sparser
"To engineer the cyclotide MCoTI-I for antagonizing protein-protein interactions between p53 and Hdm2 or HdmX we used the phage-selected α-helical peptide PMI ( xref ). xref This peptide conserves the residues Phe19, Trp23 and Leu26 of p53 required for the interaction with Hdm2 and HdmX, and is able to bind the p53 binding domains of Hdm2 and Hdmx with low nM affinity. xref The PMI peptide was grafted onto the cyclotide scaffold using loop 6."
sparser
"There is great interest in molecules that inhibit interactions between p53 and its negative regulators hDM2 and hDMX, as these molecules have validated potential against cancers that overexpress one or both of these oncoproteins. xref , xref We reported that substituted β 3 -peptides can inhibit these interactions xref , xref and, more recently, that minimally cationic β 3 -peptides are sufficiently cell permeable to upregulate p53-dependent genes in live cells. xref , xref These observations, coupled with the established intracellular stability of β-peptides xref – xref and the recently reported structures of hDM2 xref and hDMX, xref motivated us to exploit computational methods to identify β-peptides with improved potency and/or selectivity."
sparser
"Changes in chemical shifts are concentrated around loop 6, which accommodates the PMI peptide segment required for the interaction with the p53-binding domains of Hdm2 and HdmX."
sparser
"Currently, how FL118 changes the biochemical properties of Mdm2–MdmX E3 complex remains an open question, even though it can be partially explained by FL118 slightly decreasing Hdm2p53 interaction and moderately increasing Hdm2HdmX interaction ( xref )."
sparser
"As a transcription factor, p53 can bind to the promoter region of the mdm2 gene to promote transcription of Mdm2 mRNA [ xref , xref ]."
sparser
"Thus, the interactions between p53, Hdm2 and HdmX are critical for complete regulation of p53 [ xref ]."
sparser
"Compounds broadly classified as chalcones have been shown to exhibit anticancer activity through multiple mechanisms, including disruption of p53 interactions with MDM2 or HDM2, xref , xref inhibition of p-glycoprotein, xref – xref and disruption of microtubule polymerization. xref – xref Many of the latter compounds were designed as analogs of colchicine and combretastatins, natural products known to bind β-tubulin."
sparser
"Here, we describe the use of a genetic selection system and encoded library of conformationally preorganized peptides to perform functional profiling of each regulator revealing specific recognition features that guide the antagonism of Hdm2p53 and Hdmxp53 interactions."
| 12 5
sparser
"The interactions of Siva1 with both p53 and Hdm2 are weakened by DNA-damage signaling, leading to the disruption of the p53-Siva1-Hdm2 complex."
reach
"The precise mechanism of the Hdm2, Siva1, and p53 complex disruption remains to be determined."
sparser
"Siva1 interacts with both p53 and Hdm2, and facilitates Hdm2-mediated ubiquitination and degradation of p53."
reach
"Together, these data suggest that DNA-damage signals disrupt the p53, Hdm2, and Siva1 complex through the activation of ATM."
sparser
"Consistent with this notion, Siva1 binds to both Hdm2 and p53 through non-overlapping regions, enhances Hdm2 interaction with p53, and promotes p53 degradation in an Hdm2-dependent manner."
reach
"Consistently, DNA damage signaling weakened the Siva1, p53, and Hdm2 complex (XREF_FIG, lane 6 versus lane 5)."
sparser
"Upon DNA damage, the interactions of Siva1 with both p53 and Hdm2 are diminished."
sparser
"The observation that Siva1 interacts with p53 and Hdm2 through non-overlapping regions is consistent with the notion that Siva1 may promote the p53-Hdm2 interaction."
reach
"XREF_BIBR To investigate how DNA damage regulates the p53, Siva1, and Hdm2 complex, ATM expression was knocked down by siRNA (XREF_FIG, lanes 7, 8 versus lanes 5, 6)."
sparser
"To test whether Siva1Δ C affects the ability of Siva1 to enhance p53-Hdm2 interaction, we tested the Hdm2-p53 interaction in the presence of Siva1 alone or Siva1 plus Siva1ΔC. As expected, the Hdm2-p53 interaction was enhanced when Siva1 was present ( xref , lane 5 versus lane 4)."
TP53 binds MDM2 and RB1. 10 / 16
1 | 15
sparser
"The p53 and pRb pathways intersect with the formation of a trimeric p53-MDM2-Rb complex."
sparser
"These results show that RB forms a trimeric complex with p53 through its binding to MDM2 in vitro."
sparser
"Interestingly, it has also been demonstrated that Mdm2 forms a trimeric pRb-Mdm2-p53 complex, with Mdm2 acting as a linker between these two transcription factors."
sparser
"Increased formation of the RB, p53, and MDM2 trimeric complex in DNA-damaged cells suggests a role in regulating p53-mediated apoptosis in response to DNA damage; there is known to be a discordance be[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
hprd
No evidence text available
sparser
"Rb, an Egr-1 target gene, forms a trimeric complex with p53 and MDM2 to prevent MDM2-mediated p53 degradation."
sparser
"It has been shown recently that RB can also bind MDM2 to form a trimeric complex with p53 and, in doing so, prevents MDM2-mediated p53 degradation and rescues the apoptotic function but not the transc[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"These results demonstrated that RB can form a trimeric complex with p53 specifically through its interaction with MDM2 in cells."
sparser
"MDM2 is thus able to interact with the two tumor suppressor proteins; the site of interaction is different and the MDM2-RB complex is indeed able to bind p53."
sparser
"Our data show that one key difference between p53 and RUNX3 is that the latter binds to the acidic domain of MDM2, a region that is adjacent to the N-terminal domain of MDM2 that interacts with p53 and pRB ( xref , xref )."
TP53 binds TP73 and MDM2. 10 / 15
| 15
sparser
"Similarly, Nutlin-3 disrupts Mdm2p73 binding in p53-deficient cells, resulting in increased transcription of the growth inhibitory or pro-apoptotic p73 responsive genes p21 , Noxa and Puma and a[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"Both mutant p53 and p73 bind MDM2, while p63 binds much more weakly."
sparser
"Treatment with Nutlin-3, which inhibits the interaction between MDM2 and p53 or p73, had no effect on the sensitivity and survival of 4T1 cells to 6-TG (data not shown) ."
sparser
"Examples of this include Hdmx that binds the disordered transcription activation domains of p53 and p73( xref ), c-Jun and c-Fos that function as part of the AP-1 complex among many others( xref )."
sparser
"In addition, small-molecule inhibitors such as Nutlin-3 and RETRA, which disrupt the interaction of p53 and p73 with MDM2, can efficiently block KSHV-induced cell proliferation and cancer progression, promoting apoptotic cell death [ xref , xref ]."
sparser
"These results indicate that although hMDM2 can interact with both p53 and p73, its inhibition of p73 transcriptional activity is not mediated by a mechanism involving p73 protein degradation."
sparser
"To seek the chemical compounds to efficiently block the KSHV-driven cell proliferation and its associated cancers, Gao and Schulz groups have shown that the small-molecule inhibitors Nutlin-3 and RETRA, which disrupt the interaction of p53 and p73 with MDM2, are efficient to individually induce apoptotic cell death in a p53 and p73-dependent manner ( xref ; xref )."
sparser
"Both p53 and p73 bind to mdm2, but only p53 is degraded through the activity of mdm2."
sparser
"We observed that the small-molecule inhibitor Nutlin-3, which disrupts the interaction of p53 and p73 with MDM2, induces apoptotic cell death in p53 wild-type, as well as p53-mutant PEL cell lines, suggesting a possible involvement of p73."
sparser
"We examine why MDM2 interacts preferentially with p53 and p73."
| 12
sparser
"The treatment of NIH3T3 cells with CoCl 2 was associated with the induction of p53-target genes p21 and Mdm2 ( Fig. S3 )."
sparser
"Mutation of TP53 gene was associated with abolished induction of p21(Waf1/Cip1) and MDM-2 proteins and resistance to apoptosis after genotoxic treatment."
sparser
"In p53 wild type cells, BCCIP knock down by RNA interference diminishes the transactivation activity of p53 without reducing the p53 protein level, inhibits the binding of p53 to the promoters of p53 target genes p21 and HDM2, and reduces the tetrameric formation of p53."
sparser
"We showed that the extent of p53 binding to the p21 and MDM2 promoters was increased in MCF7 cells upon treatment with doxorubicin or camptothecin ( xref , bottom panels, compare lanes 1 and 7 with lanes 3, 5, 10, and 12, respectively)."
sparser
"In HMECs infected with HCMV-DB, we observed decreased binding of p53 to endogenous p53-responsive promoters of p21 and MDM2 genes as shown by chromatin immunoprecipitation ( Fig. 3 c)."
sparser
"High p53 expression levels are associated with elevated Mdm2 levels and a loss of p21(Waf1/Cip1) expression suggesting a changed functionality of p53."
sparser
"Furthermore, overexpression of mdm2, which directly interacts with the p53 and p21 promoters, results in uncontrolled cell transition to the S phase and their transformation [24, 29– xref , xref , xref , xref ]."
sparser
"Consistently, ChIP-PCR showed significantly reduced p53 binding to the p21 and MDM2 promoters in LFS OBs ( xref )."
sparser
"p53 β binds preferentially the p53-responsive promoters p21 and Bax rather than Mdm2, whereas p53 binds preferentially to Mdm2 and p21 rather than Bax promoters."
sparser
"For example, p53 β bound preferentially to BAX andp21 WAF1 promoters rather than MDM2 promoter, whereas p53 bound preferentially top21 WAF1 and MDM2 promoters than to BAX promoter [ xref ]."
| 12
sparser
"We found no evidence that MDM2 gene SNP309 or p53 gene SNP72 is associated with an increased risk for, or accelerated formation of, diffuse-large B-cell lymphoma in men or women of central European Caucasian ethnicity."
sparser
"We found an association of p53 codon72 arginine and MDM2 SNP309 GG genotype with different clinical and histological grades, human papillomavirus (HPV) infection, and age at the time of diagnosis of cervical cancer."
sparser
"The present meta-analysis indicated that the 2 gene polymorphism loci MDM2 SNP309 and p53 Arg72Pro were significantly associated with the HCC risk."
sparser
"We analyzed the interaction of TP53 R72P and MDM2 SNP309 SNPs in relationship to outcome in patients with myelodysplastic syndromes (MDS)."
sparser
"In contrast with several case-series studies, the interaction between MDM2 SNP309 and TP53 mutation was not statistically significant in our LFS family cohort."
sparser
"In conclusion, in this large collaborative study, we did not find an association of MDM2 SNP309 and TP53 R72P, separately or in interaction, with breast cancer."
sparser
"Although the contribution of MDM2 SNP309 to cancer incidence became substantially greater when both germ-line p53 and gender were incorporated into the model, the interaction between MDM2 SNP309 and p53 mutations was not statistically significant in our analyses."
sparser
"There were twelve studies that investigated the interaction of MDM2 SNP309 and p53 codon72 polymorphism on cancer risk; however, only six studies [ xref , xref , xref , xref , xref , xref ] offered detailed data (Table xref )."
sparser
"In the present study, an analysis of 102 cases that were not type II demonstrated a significant interaction between the MDM2 SNP309 and TP53 Arg72Pro polymorphism with endometrial cancer risk."
sparser
"In this meta-analysis, we pooled the eligible studies for association of MDM2 SNP309 and p53 Arg72Pro on tumor risk."
RPS3 binds TP53 and MDM2. 10 / 12
| 12
sparser
"Our findings show that RPS3 interacts with both p53 and MDM2."
sparser
"The results from our DNA pull-down assay offers the intriguing possibility that the presence of 8-oxodG in damaged DNA could act as staging position for the interaction of RPS3 with p53 and MDM2."
sparser
"What remains to be seen is how the interaction between RPS3, p53 or MDM2 affects genomic stability, especially at sites of 8-oxodG"
sparser
"We therefore tested whether the interaction between RPS3 and p53 or MDM2 intensified under oxidative stress."
sparser
"As a final means of establishing the interaction between RPS3 and p53-MDM2, we employed in situ PLA."
sparser
"We used confocal microscopy to test that the interaction between RPS3, MDM2, and p53 takes place at a single cell level."
sparser
"In an attempt to identify other novel proteins that interact with MDM2, we performed a co-precipitation of proteins bound to a biotinylated MDM2 peptide attached to streptavidin beads in which ribosomal protein S3 (RPS3) was one of the two proteins captured, and subsequently led to the discovery that RPS3 also interacts with p53 to protect it from MDM2-mediated ubiquitination."
sparser
"To understand at a greater depth the nature of the interaction between RPS3 and p53 or MDM2, we used the cis -imidazoline analog Nutlin-3, which is known to be a potent inhibitor of the MDM2 interaction with p53 [ xref ]."
sparser
"RPS3 interacts with MDM2 and p53."
sparser
"Our in vitro and in vivo data suggest that at least one biological endpoint of the interaction of RPS3 with p53 and MDM2 is to protect p53 from MDM2-mediated ubiquitination."
TP53 binds FHIT and MDM2. 10 / 11
| 9 2
sparser
"Since there is a possibility that FHIT and p53 might interact with MDM2 in a competitive way, we have also investigated the interaction of triple protein complex FHIT, MDM2 and p53 in two stages."
sparser
"Constructing these important FHIT segments and subsequently utilizing them will provide further in vitro data regarding FHIT-MDM2-p53 interaction in cancerous cell."
sparser
"Docking results indicate that interaction of full FHIT with p53 (E-total: -568.66) and MDM2 (E-total: -459.53) is accompanied with lower total energy compared to the interaction of the complete MDM2 with p53 (E-total: -399.25)."
sparser
"Thus, finding the recognition site of FHIT-MDM2 interaction with p53 binding, one can assess the interaction and/or competition among these proteins for a therapeutical approach."
sparser
"Since there is a probability that FHIT and p53 might interact with MDM2 in a competitive way, we have also examined the interaction of triple protein complex FHIT, MDM2 optimized model and p53 optimized part in two stages."
sparser
"Thus, it is logical to consider that FHIT and p53 have binding sites on MDM2 and perhaps these proteins could influence each other in binding to MDM2."
sparser
"Studies have confirmed FHIT interaction with p53 or MDM2, although functional interacting domains of FHIT with MDM2 and/or p53 are not completely defined."
sparser
"The results of our previous docking study indicate that interaction of full FHIT with p53 (E-total: -568.66) and MDM2 (E-total: -459.53) is associated with lower total energy compared to the interaction of the complete MDM2 with p53 (E-total: -399.25)."
sparser
"Accumulating evidences indicate FHIT interaction with p53 or MDM2; however, there is no certain study deciphering functional domains of FHIT involving in the interaction with MDM2 and/or p53."
reach
"In addition, a comparison of the interaction site and functional domains in regard to expression rate and/or destruction of p53 will shed light on the molecular mechanism of the FHIT, MDM2, and p53 complex."
TP53 binds MDM2 and PTK2. 10 / 10
| 10
sparser
"The recent report confirmed direct binding of the N-terminal domain of FAK with p53 and also found interaction of FAK and Mdm-2 providing a novel mechanism of FAK-Mmd-2-mediated ubiquitination of p53 in the nucleus ( xref )."
sparser
"NF2 regulates the FAKp53 and MDM2p53 interaction."
sparser
"The authors demonstrate the regions of FAK that bind Mdm-2 and p53."
sparser
"Another group showed that FAK binds p53 and also that FAK binds Mdm-2 to increase ubiquitination and degradation of p53 [ xref ]."
sparser
"Inhibition of FAKp53 and MDM2p53 interactions were evaluated in five mesothelioma cell lines including MESO924, MESO257, MESO296, MESO428, and JMN1B, at 48 h after treatment with nutlin-3 and/or at 72 h post infection with FAK shRNA ( xref )."
sparser
"Our results also indicate that NF2 regulates the interaction of FAKp53 and MDM2p53."
sparser
"The same strategy can be used to target interaction with FAK and p53, FAK and Mdm-2 and combination therapy approaches can be applied."
sparser
"The recent report confirmed direct binding of the N-terminal domain of FAK with p53 and also found interaction of FAK and Mdm-2 providing a novel mechanism of FAK-Mmd-2-mediated ubiquitination of p53 in the nucleus [ xref ]."
sparser
"Combination inhibition of the FAKp53 and MDM2p53 interactions suppressed cell viability in mesothelioma."
sparser
"The same strategy was used to target interaction with Mdm-2 and FAK (M-drugs) and p53 and FAK (P drugs)."
Mutated TP53 binds MDM2. 9 / 9
| 9
reach
"Upon combined ReACp53 and Nutlin -3 treatment, p53 levels were higher, supporting the idea that the now properly folded mutant p53 can interact with MDM2 (XREF_SUPPLEMENTARY)."
reach
"Mutant p53 and MDM2 complex is deficient in catalyzing ubiquitin release from the activated E2 conjugating enzyme."
reach
"However, these same p53 mutants formed a complex with MDM2 and were efficiently ubiquitinated, exported from the nucleus, and degraded when co-expressed with MDM2 and wild-type p53."
reach
"As MDM2 can bind both mutant p53 and TA/DeltaNp73alpha, these results indicate that p53/MDM2/p73alpha can form a trimeric complex, and that the p53 and TAp73alpha or p53 and DeltaNp73alpha interaction is enhanced by MDM2."
reach
"Knock-down of HSP90 or pharmacologic inhibition with 17-allylamino-17-demethoxygeldanamycin (17-AAG) resulted in a release of Hsp90 from mutant p53 bound to MDM2 allowing ubiquitination and degradation [XREF_BIBR]."
reach
"Here we show that in the mutant p53 and MDM2 complex, the mutant p53 core domain binds to the MDM2 acidic domain with significantly higher avidity compared to wild type p53."
reach
"23 One of the key regulators of p53 function is MDM2, which also binds to mutant p53 through the N-terminal binding regions in both proteins."
reach
"Both mutant p53 and p73 bind MDM2 well, whereas p63 binds much more weakly."
reach
"Mutant p53 interacts with MDM2."
TP53 binds MDM2 and NH. 9 / 9
| 9
sparser
"As mentioned above, MDM2 bound to NH 2 -terminal transactivation domain of p53 to destabilize and also inactivate p53."
sparser
"MDM2, which is a RING-finger type E3 ubiquitin protein ligase, bound to NH 2 -terminal transactivation domain of p53, ubiquitylated COOH-terminal 6 Lys residues (Lys-370, Lys-372, Lys-373, Lys-381, Lys-382, and Lys-386), and thereby targeting p53 for proteasome-dependent degradation [ xref ]."
sparser
"The NH 2 terminus of MDM2 protein binds to p53 and represses p53-mediated transcriptional activity [ xref ], whereas its COOH terminus contains a RING finger domain that is an E3 ubiquitin ligase, thus promoting p53 ubiquitination and proteasomal degradation [ xref ]."
sparser
"It has been shown that MDM2 tightly binds to NH 2 -terminal transactivation domain of p53 and inhibits its transcriptional as well as pro-apoptotic function [1] ."
sparser
"MDM2 directly binds to the NH 2 -terminal transactivation domain of p53 to inhibit its transcriptional activity and shuttles p53 out from the nucleus."
sparser
"As mentioned above, MDM2 binds to the NH 2 -terminal region of p53 and inhibits its transcriptional as well as pro-apoptotic function."
sparser
"As mentioned above, MDM2 binds to NH 2 -terminal transactivation domain of p53 and strongly blocks its transcriptional as well as pro-apoptotic ability [ xref ]."
sparser
"MDM2 binds to the NH 2 -terminal transactivation domain of p53 and catalyzes the addition of ubiquitin to a cluster of six COOH-terminal Lys residues (Lys-370, Lys-372, Lys-373, Lys-381, Lys-382 and Lys-386) in p53 [ xref , xref ]."
sparser
"It has been shown that p53 interacts with the NH 2 -terminal 58 aa of hMDM2, since removal of this segment abolishes this interaction ( xref )."
TP53 binds MDM2 and RITA. 8 / 8
| 8
sparser
"RITA prevented p53-HDM-2 interaction in vitro and in vivo and affected p53 interaction with several negative regulators."
sparser
"If MDM2 overexpression occurs, several compounds have been developed which can block the interaction between MDM2 and p53 like RITA (reactivation of p53 and induction of tumor cell apoptosis; binds th[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"RITA prevented interaction of p53 and Mdm-2 in vitro due to p53 conformational change ( xref )."
sparser
"Based on the previous reports on the apoptotic effect of RITA on different types of solid tumors, RITA-induced apoptosis is thought to be mediated by inhibition of the p53-MDM2 interaction by binding of RITA with p53 xref , xref – xref ."
sparser
"Interfering in the MDM2p53 interaction, with small molecules like RITA and Nutlin-3, provides an attractive strategy for (re)activating wild-type p53 in a non-genotoxic way."
sparser
"Inhibition of GSK-3β activity ( xref ) or knock down of GSK-3β ( xref ) leads to upregulation of MDM2 and degradation of p53 which could not be significantly altered by addition of inhibitors of MDM2-p53 interaction, nutlin-3a or RITA ( xref )."
sparser
"Thus, the possibility that RITA binds to both p53 and MDM2 makes it an attractive lead compound for further development of potent and effective anti-cancer drugs."
sparser
"Multiple techniques have been used to probe the binding of small molecule inhibitors RITA and Nutlin-3 to N-terminal p53 (Np53) and N-terminal MDM2 (N-MDM2), respectively."
RNF2 binds TP53 and MDM2. 7 / 7
| 6 1
sparser
"We also investigated a possible mechanism to explain the effect of RNF2 on p53 and found that RNF2 directly binds with both p53 and MDM2."
sparser
"Importantly, we found that RNF2 directly binds with both p53 and MDM2 and promotes MDM2-mediated p53 ubiquitination."
sparser
"When examining the interaction between RNF2, p53 and MDM2, we found that RNF2 can bind with both p53 and MDM2 to form a ternary complex."
reach
"Notably, the existence of the RNF2, p53, and MDM2 complex was also detected under normal conditions (XREF_FIG)."
sparser
"RNF2 directly binds with p53 and MDM2, and promotes MDM2-mediated ubiquitination."
sparser
"In the same overexpression system, we also found that RNF2 binds with both p53 and MDM2 to form a ternary complex ( xref )."
sparser
"RNF2 can bind with both p53 and MDM2 to form a ternary complex ( xref ), suggesting that RNF2 might also be a regulator of MDM2."
TP53 binds TRIM28 and MDM2. 7 / 7
| 6 1
sparser
"MAGE proteins bind to KAP1 and enhance formation of the KAP1-MDM2-p53 complex, leading to suppression of p53-mediated apoptosis and promotion of tumor cell survival ( xref )."
sparser
"TRIM28 interacts with MDM2 resulting in an enhanced deacetylation of p53 and a reduced transcriptional activity [ xref ]."
sparser
"Kap1 also interacts with Mdm2 and p53 ( xref )."
reach
"MAGE proteins bind to KAP1 and enhance formation of the KAP1, MDM2, and p53 complex, leading to suppression of p53 mediated apoptosis and promotion of tumor cell survival."
sparser
"Moreover, the formation of TRIM28-MDM2-p53 complex is enhanced by class I MAGE proteins (MAGE-A, MAGE-B and MAGE-C protein families), which are highly expressed in various cancers [ xref ]."
sparser
"Our earlier findings, for instance, show that TRIM28 may interact with MDM2 to influence the levels of the tumor suppressor p53 and this may account for significantly poorer 5-year overall survival and 5-year ‘recurrence-free’ survival seen in TRIM28 high ratio colorectal cancer patients [ xref ]."
sparser
"Treatment with actinomycin D, but not with camptothecin, augmented the interaction of p53 with Mdm2 and KAP1."
TP53 binds YY1 and MDM2. 7 / 7
| 7
sparser
"Importantly, the tumor suppressor p14ARF compromises the Hdm2-YY1 interaction, which is important for YY1 regulation of p53."
sparser
"We identify direct physical interactions of YY1 with Hdm2 and p53 and show that the basis for YY1-regulating p53 ubiquitination is its ability to facilitate Hdm2-p53 interaction."
sparser
"YY1 directly interacts with both p53 and Mdm2, a ubiquitin E3 ligase, and enhances Mdm2-mediated p53 ubiquitination and degradation. xref , xref YY1 depletion leads to either apoptosis or cell cycle arrest, depending on the cell types. xref , xref , xref Importantly, this regulation is independent of the transcriptional activity of YY1 because a YY1 mutant deficient in DNA binding retains the ability to stimulate p53 ubiquitination, and purified YY1 protein can promote p53 ubiquitination in vitro . xref A previous study indicated that YY1 promotes the expression of cytochrome c oxidase subunit 7C, regulating mitochondrial respiration. xref Recently, Yu et al xref demonstrated that this activation is mediated by the YY1-recruited deubiquitination enzyme BAP1 to the cytochrome c oxidase subunit 7C promoter."
sparser
"Interestingly, Yy1 can form transcription factor complex with both p53 and Mdm2 (), suggesting that Yy1 indirectly regulates p53-dependent cell cycle regulation leading to eventual sequestration of p5[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"201–295, mainly 226–295, xref ), and because YY1 and Hdm2 interact with p53 through different regions (a."
sparser
"YY1 forms a ternary complex with Mdm2 and p53 to promote Mdm2-mediated p53 ubiquitination and degradation. xref In addition, YY1 interacts with many other proteins directly regulating tumorigenesis."
sparser
"YY1 directly binds to both Hdm2 and p53 and enhances p53 ubiquitination and degradation, thus YY1 is a negative regulator of p53 ( xref )."
SNAI2 binds TP53 and MDM2. 7 / 7
| 4 3
reach
"In addition, wild type p53 upregulates MDM2 and forms a p53, MDM2, and Slug complex to degrade Slug in non-small-cell lung cancer cells, and Slug expression level correlates positively with lung adenocarcinoma metastasis in HCC patients XREF_BIBR."
reach
"The study suggested that wt p53 can bind to MDM2 and Slug simultaneously to form a p53, MDM2, and Slug complex, which then facilitates MDM2 mediated degradation of Slug [XREF_BIBR]."
sparser
"The study suggested that wt p53 can bind to MDM2 and Slug simultaneously to form a p53-MDM2-Slug complex, which then facilitates MDM2-mediated degradation of Slug [ xref ]."
sparser
"Recent reports have indicated that p53 also controls Slug levels, binding it together with Mdm2 to form the Mdm2-p53-Slug complex, which facilitates the Mdm2-induced degradation of Slug [25] ."
sparser
"Slug interactions with the p53 protein are believed to be mediated via Mdm2, with formation of a wild type p53-Mdm2-Slug complex leading to degradation of Slug ( xref )."
sparser
"In addition, wild type p53 upregulates MDM2 and forms a p53-MDM2-Slug complex to degrade Slug in non-small-cell lung cancer cells, and Slug expression level correlates positively with lung adenocarcinoma metastasis in HCC patients xref ."
reach
"This was shown to occur through a p53, Mdm2, and Slug complex; interestingly, mutant and transcriptionally-inactive p53 inactivates the Mdm2 mediated degradation of Slug [XREF_BIBR]."
TP53 binds RFWD3 and MDM2. 7 / 7
| 4 3
sparser
"We found that an E3 ubiquitin ligase RFWD3 (RNF201/FLJ10520) forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 and is required to stabilize p53 in the late response to DNA damage."
sparser
"RFWD3 is an E3 ubiquitin ligase that controls p53 stability by forming a RFWD3-MDM2-p53 complex, thereby protecting p53 from degradation by MDM2 polyubiquitination. xref xref The role of p53 in the pathogenesis is on interest in this context as well."
sparser
"The RFWD3 protein is an E3 ubiquitin ligase that positively regulates p53 stability by forming an RFWD3MDM2p53 complex, thereby protecting p53 from degradation by MDM2-mediated polyubiquitination xref ."
reach
"RFWD3 is an E3 ubiquitin ligase that positively regulates p53 stability by forming a RFWD3, MDM2, and p53 complex, thereby protecting p53 from degradation by MDM2 polyubiquitination XREF_BIBR, XREF_BIBR."
sparser
"RFWD3 is an E3 ubiquitin ligase that positively regulates p53 stability by forming a RFWD3-MDM2-p53 complex, thereby protecting p53 from degradation by MDM2 polyubiquitination xref , xref ."
reach
"RFWD3 is an E3 ubiquitin ligase that controls p53 stability by forming a RFWD3, MDM2, and p53 complex, thereby protecting p53 from degradation by MDM2 polyubiquitination."
reach
"The RFWD3 protein is an E3 ubiquitin ligase that positively regulates p53 stability by forming an RFWD3, MDM2, and p53 complex, thereby protecting p53 from degradation by MDM2 mediated polyubiquitination XREF_BIBR."
TP53 binds MDM2 and NUMB. 7 / 7
| 6 1
reach
"In addition, the tumor suppressor role of Numb was demonstrated to be associated with the formation of the Numb, TP53, and MDM2 complex."
sparser
"Numb forms a tricomplex with p53 and its negative regulator, MDM2."
sparser
"This study also reported that Numb forms a tricomplex with p53 and MDM2."
sparser
"Lately, it was found that NUMB can form a tricomplex with p53 and its negative regulator MDM2 which prevents its degradation [23] ."
sparser
"Among these regulators, Numb is most similar to TSC-22 because Numb binds to p53 and HDM2, thereby preventing ubiquitination and degradation of p53 xref ."
sparser
"For example, Numb forms a tripartate complex with p53 and mdm2 and in so doing stabilizes p53 against ubiquitination and proteasomal degradation (Colaluca et al. xref )."
sparser
"HBeAg and its precursors could disrupt p53-NUMB and HDM2-NUMB interactions and tricomplex p53-HDM2-NUMB formation, inhibit the acetylation and translocation of p53 from cytosol to the nucleus, promote HDM2-mediated ubiquitination and degradation of p53, and suppress p53-dependent apoptosis."
TP53 binds HBP1 and MDM2. 7 / 7
| 7
sparser
"As shown in xref B , overexpression of HBP1 disrupted the interaction between exogenous p53 and Mdm2 ( left panel ), whereas knockdown of HBP1 enhanced exogenous p53 interaction with Mdm2 ( center panel )."
sparser
"As shown in xref B , the exogenous HBP1 also interacted with both exogenous p53 and Mdm2 in H1299 cells."
sparser
"The following reciprocal GST pulldown assay further testified to the interaction between HBP1 and p53 or Mdm2 in vitro ."
sparser
"It has been found that HBP1 inhibits TCF4 transcriptional activation by interacting with TCF4 through its repression domain ( xref ), and because HBP1 interacts with the p53 binding domain of Mdm2, we assumed that HBP1 also inhibited the interaction of Mdm2 and p53 by its repression domain."
sparser
"To determine whether the interaction between HBP1 and p53 or Mdm2 is a direct interaction, we conducted a GST pulldown assay with purified His-HBP1, His-p53, His-Mdm2, GST-HBP1, GST-p53, GST-Mdm2 proteins."
sparser
"In summary, it can be concluded that HBP1 directly interacts with both p53 and Mdm2 in vivo and in vitro ."
sparser
"As shown in xref A , the endogenous HBP1 interacted with both endogenous p53 and Mdm2 in A549 cells."
TP53 binds GNL3 and MDM2. 7 / 7
| 7
sparser
"By contrast, the NS-MDM2 and MDM2-p53 interactions were unaffected by the coexpression of p53 or NS, respectively ( xref and xref )."
sparser
"The MDM2 interaction with p53 was partially reversed in I3C-treated cells after knockdown of nucleostemin, suggesting that in the absence of nucleostemin, MDM2 can still interact with p53, although at lower efficiency."
sparser
"To define the interaction between NS, MDM2, and p53, HEK293 cells were triple-transfected with HA-tagged NS, FLAG-tagged MDM2, and/or Myc-tagged p53 expression plasmids, and immunoprecipitated with anti-tag antibodies."
sparser
"Co-immunoprecipitations revealed that I3C treatment of 10AT-Her2 cells strongly promoted nucleostemin binding to the MDM2 inhibitor of the p53 tumor suppressor, and thereby sequestered MDM2 into the nucleolus."
sparser
"Although it was previously reported that NS could directly interact with p53 xref , the functional meaning of this interaction had been obscure until the binding of NS to the p53 repressor, MDM2, was revealed later on xref ."
sparser
"To assess whether the I3C regulation of MDM2 protein interactions with p53 and/or nucleostemin occurs in other indole-carbinol-sensitive breast cancer cells, three well-established cell lines, SKBR3, MCF-7 and MDA-MB-231, were treated with or without I3C for 48 hours and MDM2–p53 and nucleostemin–MDM2 co-immunoprecipitations carried out as described above for 10AT-Her2 cells."
sparser
"Therefore, the effects of I3C on nucleosteminMDM2 and MDM2p53 interactions that we observed with 10AT-Her2 cells is not limited only to this newly developed breast cancer cell line."
TP53 binds ZNF668 and MDM2. 6 / 6
| 6
sparser
"ZNF668 interacts with MDM2 and p53."
sparser
"These results identified the interaction domain of ZNF668 required for the interaction between MDM2, p53, and ZNF668 and indicated the importance of the nucleolar localization of ZNF668 for its interactions with MDM2 and p53."
sparser
"Our findings further suggest that ZNF668 regulates MDM2 through a direct interaction between ZNF668 and MDM2-p53 complex since ZNF668 interacted with MDM2 and p53 in vivo and in vitro and since ZNF668 interfered with the MDM2-p53 interaction."
sparser
"We found that addition of purified ZNF668 protein decreased MDM2-p53 binding in a dose-dependent manner ( xref )."
sparser
"The interactions between ZNF668, p53, and MDM2 were further confirmed by reciprocal immunoprecipitation using ZNF668, p53, and MDM2 antibodies ( xref ), supporting the physical interactions among these three proteins in cells."
sparser
"Since ZNF668 binds to MDM2 and p53, we next sought to determine whether there is a causal relationship between ZNF668 status and p53 protein levels."
TP53 binds MDM2 and PKM. 6 / 6
| 6
sparser
"PKM2 directly binds with both p53 and MDM2, and promotes p53 ubiquitination."
sparser
"PKM2 could directly bind with both p53 and MDM2 and promote MDM2-mediated p53 ubiquitination."
sparser
"Interestingly, we found that PKM2 could bind with both p53 and MDM2 (Figure xref and xref )."
sparser
"To study how PKM2 regulated p53 stability and ubiquitination, we next examined whether PKM2 could interact with p53 and MDM2."
sparser
"In our study, we demonstrated that PKM2 could directly bind with both p53 and MDM2 to form a ternary complex to promote p53 ubiquitination, thereby promoting its degradation (Figure xref )."
sparser
"Reciprocally, p53 also could bind with PKM2 and MDM2 (Figure xref and xref )."
HSP90 binds TP53 and MDM2. 6 / 6
| 6
sparser
"Indeed, we have already highlighted above that p53 mutants can be stabilized in cells notably via the formation of MDM2-Hsp90-p53 complex leading to MDM2 inhibition."
sparser
"Previous studies showed that in tumor cells, chaperone protein HSP90 interacts with mutant p53 to form MDM2-p53-HSP90 complex and consequently stabilizes mutant p53 xref , xref , xref ."
sparser
"In particular, in the heterozygous form, many mutant p53 proteins show a dominant-negative effect via heterotetramerization with WT p53, preventing its normal checkpoint functions. xref Second, many p53 mutants acquire gain-of-function oncogenic activities, promoting cell survival, proliferation, invasion, migration, chemoresistance, tissue remodeling, chronic inflammation, as well as inactivation of p53 paralogs p63 and p73, which belong to the same p53 tumor suppressor family and are important tumor suppressors. xref , xref Not surprisingly, tumors depleted of the WT p53 gene retain the mutant form of the protein and thus gain a selective advantage. xref Importantly, although p53 mutations are present in approximately 50% of cancers, in almost all cases where WT p53 is retained, its tumor suppressor function is eliminated via direct binding of two main p53 binding protein groups: (1) cellular mouse double minute 2 homolog (MDM2) or transformed mouse 3T3 cell double minute 4 (MDM4: also known as MDMX), xref , xref or (2) proteins encoded by DNA viruses such as the E6 protein of high-risk human papillomavirus (HPV). xref Finally, mutations in the conformation-sensitive core domain of p53 induce the association of p53 with chaperone proteins such as heat shock protein 90 (Hsp90) forming a complex p53-Hsp90-MDM2 and provoking the MDM2 inhibition leading to the stabilization of p53 mutants. xref "
sparser
"As Hsp90 binds to MDM2 and p53, xref , xref and MDM2 binds to p53 and MDMX, xref we determined whether 17AAG could affect these interactions."
sparser
"However, to be functional this complex requires an interaction with HDAC6. xref This is why an OV bearing a p53 transgene and a shRNA sequence against HDAC6 could be useful to impair the complex MDM2-Hsp90-p53 formation and promote the degradation of p53 mutants by MDM2 or by other chaperone-associated E3 ubiquitin ligase such as CHIP. xref , xref OV-p53 also could be combined with other molecules capable of blocking the pathways regulated by mutant p53."
sparser
"Prior work investigating mutant p53 stability has demonstrated a strong link to Hsp90-mutant p53 interaction, which has been shown to block MDM2-dependent ubiquitination in various cancer cell lines ( xref )."
TP53 binds HIF1A and MDM2. 6 / 6
| 6
sparser
"Competition between p53 and HIF-1 for the coactivator p300 [17] as well as MDM2-dependent degradation of HIF-1α via the formation of a complex containing p53, HIF-1α and MDM-2 [18] may explain t[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"Mdm2-mediated binding of p53 to HIF-1α causes ubiquitination and degradation of HIF-1α [19,28] ."
sparser
"Interestingly, HIF-1α also binds to the p53-binding site in MDM2, and Nutlin-3 was shown to block the MDM2-HIF-1α interaction, leading to the decreased transcriptional activity of HIF-1α and the down-regulation of its target gene VEGF under conditions of normoxia or hypoxia ( xref )."
sparser
"Mayo and colleagues used mapping and competition studies to show that HIF-1α binds the p53-binding domain of MDM2 [ xref ]."
sparser
"Conversely, p53-independent binding of MDM2 to HIF-1α was associated with the increase in HIF-1α protein content ( xref ), warning that the role of MDM2 in HIF-1α regulation might be more ambiguous than initially described."
sparser
"MDM2-mediated interaction between p53 and HIF1α affecting their stability and activity has been reported xref , xref ."
TP53 binds MDM2 and PML. 6 / 6
| 6
sparser
"In this study, we report an in vivo and in vitro interaction between PML and MDM2 which is independent of p53."
sparser
"PML may form trimeric PML-MDM2-p53 complexes and stabilize p53 in UV-damaged cells ( Kurki et al., 2003 )."
sparser
"We reported previously an in vivo and in vitro interaction between PML and MDM2 that is independent of p53."
sparser
"Similarly, the Big MAP Kinase 1 (BMK1) down-regulates PML protein levels by phosphorylating PML at S403 and T409 and promoting its degradation, thereby disrupting the interaction between PML and Mdm2 and suppressing p53 activity [ xref , xref ]."
sparser
"Interestingly, PML can bind to Mdm2 and p53 [22,72,73] , and Mdm2 and PML can form trimeric complexes, which may prevent Mdm2-mediated p53 degradation [22] ."
sparser
"BMK1 associates with PML and disrupts the interaction between PML and MDM2 (the major E3 ubiquitin ligase for p53), which leads to p53 stabilization."
TP53 binds MDM2 and PSME3. 6 / 6
1 | 5
sparser
"A homopolymer form of PA28γ interacts with both MDM2 and p53 proteins and facilitates their physical interaction, which promotes ubiquitination- and MDM2-dependent proteasomal degradation of p53, thus limiting its accumulation and resulting in inhibited apoptosis after DNA damage."
hprd
No evidence text available
sparser
"The polymer form of PA28γ interacts with both MDM2 and p53 proteins and facilitates their physical interaction."
sparser
"The polymer form of PA28gamma interacts with both MDM2 and p53 proteins and facilitates their physical interaction."
sparser
"PA28γ binds to MDM2 and p53, and promotes the MDM2p53 interaction."
sparser
"We have further defined the regions that are essential for the binding of PA28γ to MDM2 and p53, both of which are within the insert region."
GST binds TP53 and MDM2. 6 / 6
| 6
sparser
"As was observed using the cell extracts ( xref ), TAFII250 stimulated the interaction between wild-type p53 and GST-Mdm2 in pull-down experiments ( xref )."
sparser
"The amount of p53 bound to GST-MDM2 was also enhanced by the addition of PA28γ in an in vitro pull-down assay ( xref )."
sparser
"Thus starting with the wild-type p53 12mer sequence, affinity was increased by >1700-fold and the optimised peptide (Fig.  xref ) inhibited full-length p53 binding to GST-HDM2 with an IC 50 of 5 nM (García-Echeverría et al., xref )."
sparser
"Confirming this hypothesis, addition of specific HDM2 inhibitor nutlin xref disrupted the interaction between p53 and GST-HDM2, but did not influence the binding of LZAP to p53 in the same reaction ( xref )."
sparser
"Phage particles displaying p53 interacted with GST-MDM2 immobilized on 96-well plates, and the interaction was inhibited by nutlin 3."
sparser
"These combined modifications resulted in a peptide that inhibited binding of p53 to HDM2-GST with IC 50 = 5 nM for representing a 1700-fold improvement in overall binding affinity."
TP53 binds MDM2 and p2. 6 / 6
| 6
sparser
"Upon activation, p53 binds to the P2 promoter of the MDM2 gene and transcriptionally induces MDM2 protein expression."
sparser
"A two-way ANOVA indicated that any TP53 mutation was significantly associated with lower P2-MDM2 mRNA levels ( P =0.014, two-way ANOVA, xref ) and did not affect the activity of the P1 promoter ( P =0.575, two-way ANOVA)."
sparser
"The p53 protein binds to the P2 promoter of the MDM2 gene and increases the rate of MDM2 transcription."
sparser
"When DNA is damaged, p53 binds to the P2 promoter of Mdm2 , which leads to increased Mdm2 levels and subsequent decreased p53 levels. xref generated point mutations in the P2 promoter that disrupt interactions with p53 ( Mdm2 P2/P2 mice) to examine the significance of the Mdm2-p53 feedback loop (Figure xref A) ( xref )."
sparser
"We have utilized ligation mediated PCR genomic footprinting in order to investigate the intra-nuclear binding of p53 to the mdm2 P2 promoter."
sparser
"P53 binds to the P2 promoter of the MDM2 gene and promotes MDM2 gene expression."
TP53 binds MDM2 and lanA1. 5 / 5
| 5
reach
"Whether the LANA, MDM2, and p53 complex is preferentially involved in ORF50 degradation still needs to be further investigated."
reach
"Our results demonstrated that the KSHV latency associated nuclear antigen (LANA) bound to both p53 and MDM2 and that the MDM2 inhibitor Nutlin-3a disrupted the p53, MDM2, and LANA complex and selectively induced massive apoptosis in PEL cells."
reach
"The use of the MDM2 inhibitor Nutlin-3a disrupts the p53, MDM2, and LANA complex inducing a specific and highly potent activation of apoptosis in PEL cells [XREF_BIBR]."
reach
"They demonstrate that formation of the LANA, MDM2, and p53 complex is relevant to maintain viral latency [XREF_BIBR]."
reach
"Such results demonstrated that Nutlin-3 is able to disrupt the p53, MDM2, and LANA complex and to suppress the anti-apoptotic activity caused by the complex created by LANA, p53, and MDM2 [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
TP53 binds RNF31 and MDM2. 5 / 5
| 5
sparser
"For example, it remains to be determined whether RNF31 directly interacts with p53 and/or MDM2 by analyzing potential interactions between purified proteins."
sparser
"Owing to a limitation of available antibodies, we needed to further explore interactions between p53, MDM2 and RNF31 using proteins with appropriate Tags for antibody detection and choose to overexpress proteins in HEK293 cells."
sparser
"RNF31 associates with the p53/MDM2 complex and increases p53 polyubiquitination in an MDM2-dependent manner."
sparser
"Furthermore, RNF31 associated with the p53/MDM2 complex and facilitated p53 polyubiquitination and degradation by stabilizing MDM2, suggesting a molecular mechanism by which RNF31 regulates cell death."
sparser
"However, it was also important to confirm interactions between p53, MDM2 and RNF31 in this system, as the known regulation of MDM2 mRNA by p53 could be a confounder when we study the effects on p53 protein stability in a system where MDM2 is derived from the endogenous gene."
TP53 binds MDM2 and ARF. 5 / 5
| 5
sparser
"ARF binds MDM2, preventing it from interacting with p53 [ xref ]."
sparser
"The function of MDM2 is in turn regulated by p19 ARF ; p19 ARF binds MDM2 to prevent degradation of p53, and thus promotes p53-dependent apoptosis [31,46] ."
sparser
"Several groups ( Kamijo et al. 1998; Pomerantz et al. 1998; Stott et al. 1998; Zhang et al. 1998 ) have found that ARF binds to MDM2 and that trimeric complexes between p53, MDM2, and ARF can form in [MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"A number of studies have revealed direct physical interactions between ARF, p53, and MDM2."
sparser
"ARF, a tumor suppressor, binds to MDM2 and promotes rapid degradation of MDM2, resulting in p53 stabilization and accumulation [ xref ]."
TP53 binds ELP2 and MDM2. 5 / 5
| 5
sparser
"STIP is associated with Mdm2 and p53 in vivo ."
sparser
"Furthermore, the STIP-Mdm2 or STIP-p53 interaction is likely to be direct, as shown by an in vitro pulldown assay with recombinant protein (Figure xref )."
sparser
"To further establish whether the association of STIP with Mdm2 and p53 occurs under natural conditions, reciprocal immunoprecipitation assays of endogenously expressed STIP proteins with anti-Mdm2 and anti-p53 antibodies were performed."
sparser
"We found that the STIP-Mdm2 or STIP-p53 interactions were also significantly reduced (Figure xref )."
sparser
"Because STIP colocalizes and interacts with USP7 in vivo , we sought to determine whether STIP also associates with Mdm2 and p53."
TP53 binds MDM2 and NCL. 5 / 5
| 5
sparser
"Previous studies had revealed that nucleolin binds Mdm2 to regulate p53 ubiquitination, and HAUSP can form a complex with Mdm2 and p53 xref xref ."
sparser
"NCL interacts with both HDM2 and P53 [ xref , xref ] to regulate P53 stability."
sparser
"Moreover, upon DNA damage, NCL forms a ternary complex with P53 and HDM2, which recruits the ubiquitin protease HAUSP."
sparser
"Analogous to NPM1, NCL interacts with MDM2, disrupting its association with p53 [ xref ]."
sparser
"Nucleolin directly interacts with Hdm2 and p53 by distinct domains in vitro."
TP53 binds NAT10 and MDM2. 5 / 5
| 5
sparser
"Taken together, these data demonstrated that NAT10 interacts with p53 and Mdm2 both in cells and in vitro ."
sparser
"These results suggested that NAT10 interacts with p53 and Mdm2 in cells."
sparser
"Immunoprecipitation experiments were performed to verify the interaction of NAT10 with mutant p53 and Mdm2."
sparser
"NAT10 interacts with p53 and Mdm2."
sparser
"Purified Flag‐NAT10 was able to interact with GST‐p53 and GST‐Mdm2 under cell‐free conditions, suggesting that NAT10 interacts directly with p53 and Mdm2 (Fig xref G)."
TP53 binds MYL6B and MDM2. 5 / 5
| 5
sparser
"Our results provide evidence that MYL6B could bind both MDM2 and p53 proteins."
sparser
"As we have proved that MYL6B could bind both MDM2 and p53 proteins, we further investigated if MYL6B could enhance the interaction between MDM2 and p53."
sparser
"But, in this study we found that MYL6B could bind both MDM2 and p53 protein, accelerate the p53 degradation and promote HCC development."
sparser
"MYL6B binds both MDM2 and p53 proteins in HCC cell line."
sparser
"Additionally, Co-IP of endogenous MDM2 and p53 proteins with anti-MDM2 and anti-p53 antibodies respectively in Huh7 manifested that endogenous MDM2 and p53 proteins could also interact with endogenous MYL6B (Fig. xref )."
TP53 binds TP53 and MDM2. 5 / 5
| 5
sparser
"These signals involve the tumor suppressor p53 protein, a central regulator of cell responses to DNA damage, and the E3 ubiquitin ligase Mdm2, that forms a feedback regulatory loop with p53."
sparser
"Arva et al ( xref ) showed that cells carrying the SNP309 GG genotype exhibited a compromised TP53 response pathway and formed transcriptionally inactive p53-MDM2 complexes in response to stress."
sparser
"Among the other key binding partners, hdm-2 forms a complex with the tumor suppressor p53, resulting in a rapid proteasome-mediated degradation of the p53 protein."
sparser
"A recent study showed that cells that harbor this genotype had a compromised TP53 response pathway and formed transcriptionally inactive p53-MDM2 complexes in response to stress [ xref ]."
sparser
"MDM2 cannot bind serine 15-phosphorylated p53, resulting in transcription of p53-dependent promoters."
TP53 binds MDM2 and TAp73α. 5 / 5
| 5
sparser
"Thus, one could argue that the conformation of the proteins forming the p53 R175H-TAp73α complex is different than the conformation of the components forming the three-body p53 R175H-TAp73α-MDM2 complex."
sparser
"In control experiments we showed that endogenous p53 R175H simultaneously interacted with endogenous TAp73α and MDM2 forming a three-body complex (Figure xref right panel)."
sparser
"Moreover, the formation of p53 R175H-TAp73α-MDM2 complex was suggested in HCT116 ( TP53 −/− ) cells with ectopic expression of each protein of the complex."
sparser
"This data suggests that the formation of p53 R175H-TAp73α-MDM2 complex could additionally decrease the cellular apoptotic response, thus increasing chemoresistance (Figure xref )."
sparser
"In the case of H1299 lung cancer cells, ectopic expression of MDM2 released HSPA1A/HSP70 and DNAJB1/HSP40 from the p53 R175H-TAp73α complex in a dose dependent manner, thus leading to the formation of p53 R175H-TAp73α-MDM2 complex (Figure xref )."
TP53 binds UBE4B and MDM2. 5 / 5
| 5
sparser
"Similarly, UBE4B having E3 and E4 ligase activities binds to p53 and MDM2 and leads to inhibition of p53 dependent apoptosis (Wu et al., xref )."
sparser
"In addition, UBE4B physically interacted with Hdm2 and p53 in vivo , and UBE4B negatively regulates p53."
sparser
"The combined results proved that UBE4B interacts with both p53 and Hdm2."
sparser
"In 2011, Wu et al. showed that UBE4B physically interacts with p53 and Hdm2 and negatively regulates p53 stability and function xref ."
sparser
"In addition, the E4 ligase UBE4B interacts physically with p53 and MDM2 to polyubiquitylate p53 (Wu et al., xref )."
| 5
sparser
"These data suggested that DNA damages affected the IRTKS-p53 and IRTKS-MDM2 interactions differently and specifically."
sparser
"Moreover, IRTKS variant with IMD deletion failed to enhance MDM2-induced p53 ubiquitination ( xref ), indicating that the IMD region which was required for the physical association of IRTKS with both MDM2 and p53, was crucial for IRTKS-induced p53 ubiquitination."
sparser
"IRTKS interacted directly with both p53 and MDM2 through its IMD domain, and enhances low level MDM2-mediated p53 ubiquitination in vivo and in vitro."
sparser
"Our data indicated that the IMD domain was required for IRTKS binding to p53 and MDM2 and for its effect on MDM2-mediated p53 ubiquitination."
sparser
"We then investigated the effect of DNA damage on the interaction of IRTKS, p53 and MDM2."
RPL11 binds RPL5, TP53, and MDM2. 5 / 5
| 3 2
sparser
"Two ribosome proteins, RPL5 and RPL11 are major mediators of this Ribi checkpoint; excess RPL5 and RPL11 bind Mdm2 and inhibit its interaction with p53, causing p53 to accumulate ( xref )."
reach
"These results suggest that RPL4 may associate with the RPL5, RPL11, MDM2, and p53 complex."
sparser
"Two ribosome proteins, RPL5 and RPL11, are major mediators of this Ribi checkpoint; excess RPL5 and RPL11 bind Mdm2 and inhibit its interaction with p53, causing p53 to accumulate ( Teng et al., 2013 [MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
reach
"RPL4 interacts with the RPL5, RPL11, MDM2, and p53 complex in cells."
sparser
"Under conditions of defective ribosome biogenesis, this apoptotic response is triggered by the ‘nucleolar stress response’, the binding of excess ribosomal proteins, such as RPL5 and RPL11, to Mdm2, which in turn prevents Mdm2 mediated p53 degradation [ xref ]."
TP53 binds phosphorylated MDM2. 4 / 4
| 4
reach
"It has been demonstrated that phosphorylated MDM2 binds p53 more efficiently than unphosphorylated MDM2."
reach
"Similarly, Akt can phosphorylate MDM2, which enhances its nuclear localization; subsequently, the phosphorylated MDM2 binds to p53 and causes degradation of p53 by ubiquitin-proteasome pathway."
reach
"Phosphorylated MDM2 binds to p53, expediting its degradation and interfering with tumor suppression effects of the later."
reach
"After DNA damage, phosphorylated MDM2 monomers may still bind p53 and recruit activated E2, and thus can promote mono ubiquitination of p53."
TP53 binds HDAC1 and MDM2. 4 / 4
| 4
sparser
"Further, it has been observed that p53 acetylation is a reversible process and for it Mdm2 recruits HDAC1 (a histone deacetylase) to form a Mdm2-HDAC1 complex which deacetylates p53."
sparser
"The HDAC1 complex binds MDM2 in a p53-independent manner and deacetylates p53 at all known acetylated lysines in vivo."
sparser
"Interestingly, the knock-down of SMAR1 using siRNA leads to a prolonged cell-cycle arrest in the post stress recovery phase due to ablation of p53-MDM2-HDAC1 interaction."
sparser
"Therefore, our finding that p53 is associated with Mdm2 and HDAC1 in MEFs that normally express p53 acetylated on Lysine 373/382 residues are intriguing."
RPL5 binds TP53 and MDM2. 4 / 4
1 | 3
hprd
No evidence text available
sparser
"For example, the p53-Mdm2 complex interacts with ribosomal protein L5 and 5S rRNA (Marechal et al., 1994) , and p53 was shown to bind to DNA sequences near replication origins in the ribosome gene cl[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"RRM1 is Required for Interaction with the RPL5-MDM2 Complex, p53 Induction, and OIS."
sparser
"On the one hand, SRSF1 overexpression leads to the formation of a nucleoplasmic complex with the ribosomal protein RPL5 and the E3-ubiquitin ligase MDM2, which normally ubiquitylates the p53 tumor-suppressor protein leading to its proteolytic degradation [ xref ]."
STUB1 binds TP53 and MDM2. 4 / 4
| 4
sparser
"Notably, co-expression of BAG5 clearly decreased the mutp53MDM2 and mutp53CHIP interaction in a dose-dependent manner ( xref )."
sparser
"Unlike wild type p53, the unfolded and aggregated mutant p53 proteins are bound by HSP90, which blocks the interaction of endogenous MDM2 and CHIP (carboxy-terminus of Hsp70-interacting protein) with mutant p53."
sparser
"The mutp53MDM2 and mutp53CHIP interaction was examined in H1299 cells transfected by expression vectors of mutp53 (R175H), MDM2, CHIP along with different amount of BAG5 by co-IP assays."
sparser
"We then investigated whether BAG5 inhibits MDM2 and CHIP-mediated mutp53 degradation through inhibiting the mutp53MDM2 and mutp53CHIP interaction."
TP53 binds MDM2 and azu. 4 / 4
| 4
sparser
"The occurrence of specific binary interactions of both Azurin and Mdm2 with p53, as investigated more appropriately in their full-length conformation, is ascertained and the corresponding association and dissociation rate constants are measured."
sparser
"Moreover, the apparent antagonist action of azurin against Mdm2, with respect of p53 regulation, might suggest the possibility that azurin binds p53 at the same site of Mdm2, preventing in such a way p53 and Mdm2 from association and thus p53 from degradation."
sparser
"Bizzarri et al. have previously reported a study on p53-MDM2 and p53-azurin interactions using such an approach xref , xref ."
sparser
"Furthermore, SPR analysis of the Azurin-p53-MDM2 ternary interaction, whose occurrence has been proposed by AFS experiments, was performed [ xref ]."
TP53 binds MDM2 and TAD1. 4 / 4
| 4
sparser
"In this case, the entropic penalty for p53-TAD1 binding to Mdm2, −Δ=+2.2–2.6kcalmol , was much smaller than the value reported herein for binding to MdmX (+8.1±0.1kcalmol; b)."
sparser
"In this case, the entropic penalty for p53-TAD1 binding to Mdm2, -TΔS = +2.2–2.6 kcal mol−1 xref , was much smaller than the value reported herein for binding to MdmX (+8.1 ± 0.1 kcal mol −1 ; xref )."
sparser
"The Mdm2:p53-TAD1 interaction has been the target of drug discovery efforts for more than a decade and compounds with low nM binding constants for the Mdm2 pocket are in clinical trials against a variety of human cancers, some of which are characterized by Mdm2 overexpression xref ."
sparser
"The Mdm2:p53-TAD1 interaction has been the target of drug discovery efforts for more than a decade and compounds with low nanomolar binding constants for the Mdm2 pocket are in clinical trials against[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
TP53 binds CISH and MDM2. 4 / 4
| 4
sparser
"The stronger binding of p53 trans to MDM2 compared to p53 cis suggests a possible mechanism to help maintain a minimal level of p53 in unstressed cells."
sparser
"The stronger binding of trans p53(17–29) to MDM2 compared to cis may suggest a mechanism to help maintain minimal levels of p53 in unstressed cells and allow for rapid response to cellular stress."
sparser
"The stronger binding of trans p53(17–29) to MDM2 compared to cis may leave a minimal level of p53 available to respond to cellular stress."
sparser
"The stronger binding of p53 trans to MDM2 compared to p53 cis may suggest a mechanism to help maintain minimal levels of p53 in unstressed cells, which could help for rapid response to cellular stress."
TP53 binds GSK3B and MDM2. 4 / 4
| 4
sparser
"In our co-immunoprecipitation study, we demonstrated that GSK-3β, p53 and MDM2 bind to each other in cytosolic and nuclear fractions of HT-22 cells ( xref )."
sparser
"To study interactions between GSK-3β, p53 and MDM2, we performed co-immunoprecipitation experiments."
sparser
"To further confirm this idea, we undertook comprehensive inhibitory approach: we genetically knocked down either MDM2 or GSK-3β with specific shRNA, or inhibited either GSK-3β or MDM2-p53 interaction with small molecule inhibitors."
sparser
"Taking together, these results demonstrate that GSK-3β inhibition decreases complex formation between GSK-3β, p53 and MDM2 suggesting that GSK-3β activity is essential for interactions between GSK-3β, p53 and MDM2 in subcellular compartments."
TP53 binds MDM2 and RING. 4 / 4
| 4
sparser
"The mRNA of p53 can interact with the RING domain of MDM2, which prevents the E3 ligase activity and furthermore stimulates translation of the p53 mRNA [ xref ]."
sparser
"Mdm2 associates with p53 polysomes via its RING domain and probably enhances translation."
sparser
"For example, the RING domain of MDM2 can bind to p53 mRNA and promote its translation ( xref )."
sparser
"Lastly, although the RING domain of MDM2 does not bind to p53 directly, it possesses E3 ligase activity and is thus responsible for ubiquitinating p53 and marking it for degradation."
TP53 binds MDM2 and NGFR. 4 / 4
| 4
sparser
"This finding explained why NGFR, MDM2 and p53 could form a ternary complex ( xref )."
sparser
"Nevertheless, our studies as shown in this manuscript do confirm that nuclear NGFR can bind to p53 and MDM2, consequently inactivating p53 by directly inhibiting its transcriptional activity and facilitating MDM2-dependent ubiquitination and degradation."
sparser
"Thus, we tested if p53 binds to NGFR directly or indirectly through MDM2."
sparser
"Demonstration of the endogenous interaction between NGFR, MDM2 and p53 in SK-N-SH cells shown in xref is central to the paper and this needs to be repeated using reciprocal IPs and cell fractionation."
| 4
sparser
"Taken together, our results propose that LZAP binds both HDM2 and p53, and regulates p53 levels in a HDM2-dependent manner."
sparser
"These results suggested that LZAP and p53 independently bind different parts of HDM2."
sparser
"To confirm and further examine LZAP binding to HDM2 and p53, complex formation was investigated using recombinant proteins in cell-free system."
sparser
"LZAP binds p53 and HDM2."
TP53 binds CDKN1A, BBC3, and MDM2. 4 / 4
| 4
sparser
"ChIP assays from HCT116 p21 −/− cells show binding of p53 at CDKN1A , MDM2 , and BBC3 which served as positive controls, but not at the promoters of Survivin , CDC25C , and PLK1 (Figure xref )."
sparser
"MDM2 suppression was associated with a marked increase in p53 and p53 effector genes p21 and PUMA transcript levels ( xref )."
sparser
"Treatment was associated with P53 stabilization and induction of MDM2, P21, and PUMA expression [ xref ]."
sparser
"Consistent with this idea, silencing of Mage-A expression leads to upregulation of several p53-responsive genes in a p53-dependent manner and stimulates by several fold the interaction of p53 with the p21, MDM2, and PUMA promoters."
| 4
sparser
"At the transactivation region, p53 interacts with TFIID, TFIIH, Mdm2, RPA, CBP/p300 and CSN5/Jab1 [ xref ]."
sparser
"At the transactivation region, p53 interacts with TFIID, TFIIH, Mdm2, RPA, CBP/p300 and CSN5/Jab1, among many other proteins [ xref ]."
sparser
"At the transactivation region, p53 interacts with TFIID, TFIIH, Mdm2, RPA, CBP/p300, and CSN5/Jab1 among many other proteins (Anderson and Appella, xref )."
sparser
"The transactivation region of p53 interacts with TFIID, TFIIH, Mdm2, RPA, CBP/p300 and CSN5/Jab1 [ xref ]."
TP53 binds mutated MDM2. 3 / 3
| 3
reach
"Cotransfecting these cells with a mutant Mdm2, which can bind to p53 but can not target it for degradation, resulted in higher p53 levels than that in cells transfected with wildtype Mdm2, even in the presence of the anoikis promoting fibronectin fragment."
reach
"Interestingly, our western blot data in XREF_FIG showed that the mutant Mdm2, which can bind to p53 but can not target it for degradation, gave the expected mutant Mdm2 band at the 37 KD position but also some high molecular weight bands."
reach
"Finally, we transfected p53 and Mdm2-null cells with wildtype p53, wildtype Mdm2 and a mutant Mdm2 (human Mdm2 Delta222-437) that binds p53 but can not target it for proteasomal degradation [XREF_BIBR, XREF_BIBR], or a combination of these."
PLK4 binds TP53 and MDM2. 3 / 3
| 3
sparser
"Moreover, the ability of oxazoloisoindolinone 3a to block the intracellular p53MDM2 interaction in HCT116 p53 +/+ cells was checked by co-IP."
sparser
"Based on the data presented here, these 6-chloroindole compounds do not target Mdm2-p53 interactions in HCT116 cells."
sparser
"Additionally, the ability of oxazoloisoindolinone 3a to block the p53-MDM2 interaction in HCT116 p53(+/+) cells was confirmed by co-immunoprecipitation."
HSPA binds TP53 and MDM2. 3 / 3
| 3
sparser
"Binding of p53 to Mdm2 and Hsp70 was not dependent on CCT interaction."
sparser
"Taken together, these results show that CCT binding is not required for p53 to bind Mdm2 or Hsp70."
sparser
"This is the case for the above mentioned p53Hsp70Mdm2 interaction [ xref ] and also for the acetyltransferase p300, a protein that contains a highly disordered region that displays similarities to prion-like domains."
TP53 binds ANKRD1 and MDM2. 3 / 3
| 3
sparser
"Interaction of ANKRD1 with MDM2 and