Property Summary

NCBI Gene PubMed Count 180
PubMed Score 182.06
PubTator Score 187.72

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (15)

Disease log2 FC p
malignant mesothelioma 1.700 1.2e-03
oligodendroglioma 1.200 2.0e-02
psoriasis -1.100 2.8e-03
osteosarcoma -2.199 1.2e-08
ependymoma 1.100 1.3e-06
group 3 medulloblastoma 1.700 6.8e-04
medulloblastoma, large-cell 1.300 3.0e-04
primitive neuroectodermal tumor 1.200 7.1e-03
juvenile dermatomyositis 1.407 1.1e-13
acute quadriplegic myopathy 1.196 3.5e-05
tuberculosis and treatment for 6 months 1.300 8.8e-06
intraductal papillary-mucinous adenoma (... 1.400 6.6e-03
diabetes mellitus -1.200 3.6e-03
Pick disease 1.100 6.2e-06
ovarian cancer -2.700 1.3e-11

 GO Component (2)

Gene RIF (141)

PMID Text
26471763 MDM4 SNP34091 status to be associated with reduced risk of breast cancer, in particular in individuals carrying the MDM2 SNP309GG genotype, but not to be associated with either lung-, colon- or prostate cancer.
26416355 Authors show that the EMT phenotype in multiple cellular models and in clinical prostate and breast cancer samples is associated with a decrease in MDM2 and increase in MDMX expression.
26274820 MDM4 rs4245739 single nucleotide polymorphism contributes to small cell lung cancer risk and support the notion that gene 3'-UTR genetic variants, impacting miRNA-binding, might modify small cell lung cancer susceptibility.
26181202 These results identify Mdmx growth dependency in wt p53 expressing breast cancer across a range of subtypes. Based on our findings, we propose that Mdmx targeting is an attractive strategy for treating breast cancer harboring wt p53
26159518 CETSA was able to validate stapled peptide binding to Mdm2 and Mdm4.
26148237 The phosphate group of pTyr99 imposes extensive steric clashes with the C-terminus of p53 peptide and induces a significant lateral shift of the peptide ligand, decreasing the binding affinity of MDMX for p53.
26028311 MDM4 mutation identified in a glioma patient was associated with loss of the putative MDM4 target site. Therefore, let-7 binding to MDM4 is implicated in the DNA damage response
25961923 MDM4/HIPK2/p53 cytoplasmic assembly uncovers coordinated repression of molecules with anti-apoptotic activity during early DNA damage response.
25825738 Data indicate that both p53-binding protein oncoprotein MDM2 and MDMX protein bind to p53 through a hydrophobic pocket at the N-terminal domain, but the interactions appear to be regulated differently.
25809483 analysis of an MDM2 C-terminal deletion mutant reveals that the C-terminal residues of MDM2 are required for both MDM2 and MDMX interaction.
25703327 MDMX exerts oncogenic activity via suppression of RB.
25670033 We show using reporter gene assays and endogenous MDM4 expression analyses that miR-191-5p and miR-887 have a specific affinity for the rs4245739 SNP C-allele in prostate cancer
25659040 hMDMX regulates its C-terminal RING domain and the hMDM2 activity.
25512388 in the absence of p53 or in the presence of MdmX overexpression, FL118 promotes p53-independent apoptosis
25405759 MDM4 overexpression is related to complex karyotype-acute myeloid leukemia with wild-type TP53 and might play a pathogenic role by inhibiting p53-signal pathway.
25394965 Finally, a strong association between the expression of EEF1A2, phosphorylated AKT and MDM4 was observed in human HCC samples. Strong activation of the EEF1A2/PI3K/AKT/mTOR/MDM4 signaling pathway was observed in HCC patients.
25372739 The authors summarized findings indicating that MDM2 and MDM4 constitute a two-gene family (MDM2 gene family) that belongs to the RING superfamily but have evolved separately from other members of the superfamily. [review]
25026175 The results indicate a putative role for the MDM4 gene in predicting local recurrence of bladder cancer.
24972690 The HDMX polymorphism is unlikely to contribute to individual susceptibility to sarcoma.
24755078 Analysis of the Mdm2 and MdmX RING domains showed that C449 of Mdm2 located at the Mdm2 RING dimer interface is critical for the stability of the RING dimer structure, while R479 has a role in recruiting and activating the ubiquitin E3 conjugating enzyme.
24667108 Mdmx may contribute to the regulation of p53 independently of Mdm2 in breast carcinogenesis
24659749 Endogenously high levels of Mdm4 inhibit and sequester p53 in AML. High levels of Mdm4 do not block function of Mdm2 inhibitors in AML.
24608433 results reveal a novel p53- and Mdm2-independent oncogenic function of Mdmx that provides new insight into the many cancers that overexpress Mdmx.
24488925 Another important mechanism by which tumors bypass TP53 functions is via increased levels of two TP53 inhibitors, MDM2, and MDM4
24445145 Loss of MDM4 expression is associated with glioblastoma.
24285179 The activation level of the EEF1A2/PI3K/AKT/mTOR/MDM4 axis significant influences the survival probability of hepatocellular carcinoma patients.
24141721 Downregulation of Mdm4 by miR-661 augments p53 activity and inhibits cell cycle progression in p53-proficient cells.
24127580 MDMX contains a regulatory element (the "WWW element") that binds to its own N-terminal domain and prevents MDMX from binding to p53.
24027430 Our data show that alternative splicing of MDM2 and MDM4 is an important feature of high-grade disease for specific types of rhabdomyosarcoma tumors.
24018792 role of full-length MDM2 and MDMX proteins and their isoforms in surgical specimens of well-differentiated/de-differentiated liposarcomas
23994448 the novel variant MDM4-B may play a role in glioma tumorigenesis or cancer progression
23946421 Data indicate that stapled alpha-helical peptide ATSP-7041 binds both MDM2 and MDMX with nanomolar affinities and activates the p53 pathway in tumors in vitro and in vivo.
23793604 Functional MDM4 rs4245739 SNP, alone and in combination with P53 Arg72Pro genetic variant, was associated with a significantly decreased risk of breast cancer in Chinese populations.
23724042 The MDM4 rs4245739 (miR-191 target site) AC and CC genotypes were significantly associated with decreased esophageal squamous cell carcinoma risk
23324352 The interaction of nutlin with MDMX is very short-lived compared with MDM2 and does not show such direct initial interactions with the binding site.
23028042 DNA damage activates p53 in part by disrupting CK1a-MDMX interaction and reducing MDMX-p53 binding affinity.
22937789 FULL length-MDM4 and a splicing variant of MDM4 overexpression are indicators of p53 aberrations in chronic lymphocytic leukemia patients, suggesting that those patients have a poor prognosis.
22916154 quantify the expression of MDM4 and MDM2 mRNA and protein in human fetal retinae, primary retinoblastomas, retinoblastoma cell lines and several independent orthotopic retinoblastoma xenografts
22870278 MicroRNA-34a modulates MDM4 expression via a target site in the open reading frame.
22845047 MDM2 protein & mRNA expression levels did not correlate with lack of TP53 genetic changes or expression. There was an inverse relationship between detectable TP53 protein expression & MDM4 copy number gains & mRNA expression.
22825724 The results of this study showed that strong association between MDM4 gene alternation and high-grade oligodendroglial tumors.
22820643 Mdm4 is upregulated in a substantial proportion of stage I-IV human melanomas. It promotes the survival of metastatic melanoma by antagonizing p53. In xenografts, inhibition of the MDM4-p53 interaction restored p53 function.
22586610 These compounds effectively inhibit the E3 ligase activity of the Mdm2-MdmX hetero-complex.
22556425 hypoxia can activate p53 through inactivation of MDMX by the ATR-Chk1-MDMX-14-3-3gamma pathway.
22490292 The rs1563828(C > T) polymorphism in MDM4 gene may not confer risk to breast cancer, especially for early-onset breast cancer patients. Homozygous TT of rs1563828 is associated with younger age of onset of breast cancer.
22410433 Current progress in the field about the functional and physical interaction between Mdm2 and Mdmx, their individual and collaborative roles in controlling p53.
22408446 Confirmation that the residue Tyr99 in MDMX can generate a steric clash with the inhibitors due to energy and structure.
22374672 The work demonstrates that the ability of MDM4 to enhance p53 stability is actually a specific property of MDM4 accomplished upon DNA damage.
22333590 The length of the C-terminal regions of MdmX proteins has been conserved in evolution, because it can influence their activity toward tumor suppressor p53.
22290440 Downregulation of MDMX results in lower levels of mature and nascent MDM2 transcripts following cellular stress.
22180099 that MDM2 and MDM4 polymorphisms may influence development and/or survival in RB.
22120712 Loss of ARF during tumor development not only prevents p53 stabilization by proliferative stress but also causes accumulation of MDMX compromising p53 activity
22040960 MDM4 is significantly higher in chronic lymphocytic leukemia patients with P53 deletion or mutation.
21910853 Our studies show that hMDMX has the essential properties of an oncogene
21823114 The risk of HPV16-associated squamous cell carcinoma of the oropharynx (SCCOP) could be modified by MDM4 polymorphisms.
21784052 MDM4 is a candidate gene for miR-10a. Validation of MDM4 in leukemic cells revealed a robust negative relationship between miR-10a overexpression & MDM4 downregulation.
21750655 A small-molecule p53 activator induces apoptosis through inhibiting MDMX expression in breast cancer cells.
21572037 MdmX protein is essential for Mdm2 protein-mediated p53 polyubiquitination.
21541195 The recently discovered p53-MDMX feedback loop, which affects the outcome of genotoxic insults in cells, is reviewed.
21540763 These results suggest that the joint effect of MDM4 variants may contribute to the risk of oropharyngeal cancer in non-Hispanic whites.
21503588 MDM4 might play a role in colorectal carcinogenesis that is not limited to negative regulation of p53 in combination with MDM2
21148311 a new role for 14-3-3gamma in protecting p21 from MDMX-mediated proteasomal turnover, which may partially account for DNA damage-induced elevation of p21 levels independent of p53.
21088494 The role of MDMX in the regulation of not only p53 but also p73 transcription factor, and possibly even p63.
21084273 Data show that acquisition of an illegitimate miR-191 target site causes downregulation of MDM4 expression, thereby significantly delaying ovarian carcinoma progression and tumor-related death.
21084273 Observational study of gene-disease association. (HuGE Navigator)
21081495 a direct link between genotoxic stress-activated c-Abl kinase signaling and Mdm2-Mdmx complex formation
20863813 these results suggest that the abundant expression of MDM4 in fibroblast-like synoviocytes may contribute to the hyperplasia phenotype of RA synovial tissues.
20855462 Importance of p53 regulators in prostate cancer development and progression.
20855462 Observational study of gene-disease association. (HuGE Navigator)
20819778 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20724842 The interaction of HdmX with p53 and the re-localization of HdmX to the nucleus through Hdm2 association appear to be required for this activity.
20713061 The authors showed that USP7 N-terminal domain recognized two of six P/AxxS motifs of HdmX ((8)AQCS(11) and (398)AHSS(401)) and also identified an additional interaction site ((397)PSTS(400)) on Hdm2.
20680659 Histone deacetylase inhibitors enhance the anticancer activity of nutlin-3 and induce p53 hyperacetylation and downregulation of MDM2 and MDM4 gene expression.
20677014 Observational study of gene-disease association. (HuGE Navigator)
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20520810 A multiplicative joint effect of MDM2 and p53 codon72 polymorphism on risk, was observed. The MDM4 polymorphism had no significant effects.
20520810 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20472715 HDMX exhibits bona fide oncogenic properties
20417304 This review summarizes the different facets of MDM4-mediated regulation of p53 and the modifications able to modulate MDM4 localization and function.
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20372076 Findings suggest that MDM2 and MDMX are responsible for the functional inactivation of p53 in testicular germ cell tumors.
20333547 MDM2, MDMX, Pirh2 and COP1 might inhibit p53 activity synergistically in vivo.
20190571 Molecular dynamics simulations have been used to explore the differences in binding of p53 and nutlin to MDM2/MDMX.
20172729 Studies indicate that both Mdm2 and Mdmx receive input from numerous signaling pathways and interact with many proteins in addition to p53.
20062013 HDM4 is overexpressed in mantle cell lymphoma and, at least in part, exerts its effect by suppressing p21 expression, thereby enhancing cell-cycle progression.
19946469 In tumor cells where both Hdm2 and HdmX are overexpressed, removal of one leads to an anti-proliferative effect in cells harboring wild-type p53 and induction of p53 cell cycle arrest genes that negatively feedback onto the E2F pathway.
19913121 Observational study of gene-disease association. (HuGE Navigator)
19838211 Data show that ectopic expression of wild-type USP2a but not a catalytic mutant prevents Mdm2-mediated degradation of MdmX.
19762336 the association of a single-nucleotide polymorphism in human MDM4 (C>T) with age of onset of breast cancer
19762336 Observational study of gene-disease association. (HuGE Navigator)
19619542 Results suggest that alteration of the substrate specificity via binding to Mdmx may contribute to efficient ubiquitination and inactivation of p53 by Mdm2.
19580521 Stochastic modeling and simulation of the p53-MDM2/MDMX loop.
19507240 analysis of different p53 recognition of MDM2 and MDMX
19497887 Association studies in 5 different patient populations reveal that these SNPs in MDM4 confer an increased risk for, or early onset of, human breast and ovarian cancers in Ashkenazi Jewish and European cohorts, respectively.
19470478 Observational study of gene-disease association. (HuGE Navigator)
19305137 Crystal structures of two complexes, a p53-like mutant peptide with the N-terminal domains of Mdm2 and Mdmx, respectively, are presented.
19255450 These findings deciphered the structural basis for high-affinity peptide inhibition of p53 interactions with MDM2 and MDMX.
19153082 Crystal Structures of Human MdmX (HdmX) in Complex with p53 Peptide Analogues Reveal Surprising Conformational Changes.
19084022 the binding pocket in the three MDM4 structures converged to a common conformation after removal of the ligands, indicating that the differences are due to induced fit. The largest conformational changes were for the MDM4 molecules bound to p53.
19075013 c-Abl not only targets Hdm2, but also Hdmx, which together contribute to p53 activation in response to DNA damage.
18826207 the presence of conserved and non-conserved interactions along the conformational transition pathway that may be exploited in the design of selective and dual modulators of MDMX activity
18785023 MDM4 gain is associated with the early transition from normal retina to retinoma.
18677113 Structure of the human Mdmx protein bound to the p53 tumor suppressor transactivation domain.
18644346 Overexpression of MDM2 and MDM4 is not a necessary step in retinoblastoma development.
18451213 data indicate that gain/amplification and overexpression of MDM4 is a novel molecular mechanism by which a subset of urothelial cell carcinoma escapes p53-dependent growth control, thus providing new avenues for therapeutic intervention.
18356162 stabilization of MDMX by Akt may be an alternative mechanism by which Akt up-regulates MDM2 protein levels and exerts its oncogenic effects on p53 in tumor cells
18335186 Levels of MDM2, MDM4, and its variants, MDM4-S (originally HDMX-S) and MDM4-211 (originally HDMX211), in a group of 57 papillary thyroid carcinomas, were estimated.
18279506 There is no evidence for a major role of MDM4 coding variants in the inherited susceptibility towards breast cancer in German patients.
18279506 Observational study of gene-disease association. (HuGE Navigator)
18172009 MDMX expression is regulated by mitogenic signaling pathways. This mechanism may protect normal proliferating cells from p53 but also hamper p53 response during tumor development.
18086887 These results demonstrate that MDMX and MDM2 independently and cooperatively regulate the proteasome-mediated degradation of p21 at the G(1) and early S phases.
17651783 Expression of both MDM2 and MDM4 in tumors without p53 mutations strongly suggests that MDM2 and MDM4 inhibit the activity of this tumor suppressor in head and neck squamous carcinomas.
17616658 the MDM2 and MDMX complex has a role in abundance and activity of p53
17159902 functions of the extreme C-terminus of MDM2 can be provided by MDMX
17110929 MDMX is an important regulator of p53 response to ribosomal stress and RNA-targeting chemotherapy agents.
17080083 amplification of the MDMX gene and increased expression of MDMX protein are strongly selected for during tumour progression as a mechanism to suppress the p53 response in RB1-deficient retinal cells
17018606 MDM4 is alternatively spliced following UV irradiation. Alternate forms of MDM4 place selective pressure on the cells to acquire additional alterations in the p53 pathway.
16943424 These results demonstrate a sophisticated control by ATM of a target protein, Hdmx, which itself is one of several ATM targets in the ATM-p53 axis of the DNA damage response.
16616333 Mdm4 regulates tumor suppressor p53 activity, while Mdm2 mainly controls p53 stability
16510145 MdmX may have different roles in the regulation of Mdm2 activity for ubiquitination of pRB and p53
16163388 ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage.
16082221 ATM directly activates p53 while activating a safe-lock mechanism to inactivate the negative regulators of p53, Mdm2, and Mdmx [review]
16027727 deletion of Mdm4 enhances the ability of Mdm2 to promote cell growth and tumor formation, indicating that Mdm4 has antioncogenic properties when Mdm2 is overexpressed
15944197 identification of functionally different alleles of genes and suggestion that the different alleles at this SNP locus in the MRP1 gene may account, in part, for inter-individual variations and population differences in drug response
15907800 sumoylation-deficient MDMX mutant undergoes normal ubiquitination and degradation by MDM2, normal nuclear translocation and degradation after DNA damage, and inhibits p53 with wild type efficiency
15906355 HDMX gene was amplified in 17% of soft tissue sarcoma patienets and gene amplification was associated with poor prognosis.
15876864 MdmX can affect post-translational modification and stability of Mdm2 and p53 activity through interaction with ARF
15788536 sites important for Hdm2-mediated ubiquitination of Hdmx after double-strand break induction
15782125 Mdm2 and mdmx prevent ASPP1 and ASPP2 from stimulating the apoptotic function of p53 by binding and inhibiting the transcriptional activity of p53.
15199139 hMdmx is overexpressed in a significant percentage of various human tumors and amplified in 5% of primary breast tumors, all of which retained wild-type p53. iRNA-mediated reduction of hMdmx inhibited cell growth potential in a p53-dependent manner
14739777 MdmX represses E2F1 transactivation
14660608 findings reveal a novel role for MDM4 protein by demonstrating that in non-tumor cells under stress conditions it may act as a positive regulator of p53 protein activity
12963717 DNA damage-induced MDMX degradation is mediated by MDM2
12860999 MDMX is ubiquinated and degraded by MDM2
12640683 mouse double minute 4 homolog gene amplification is associated with malignant gliomas on 1q32
12483531 Smad-induced transactivation by MdmX occurs by altering Smad interaction with its coactivator p300
12393902 MdmX is a RING finger ubiquitin ligase capable of synergistically enhancing Mdm2 ubiquitination
12370303 MDMX is transported to the cell nucleus upon DNA damage with or without p53
12162806 MDMX dramatically inhibits the acetylation of p53 induced by both endogenous and ectopically expressed p300/CBP.
11953423 MDMX, when exceedingly overexpressed, inhibits MDM2-mediated p53 degradation by competing with MDM2 for p53 binding
11840332 stability is regulated by p53-induced caspase cleavage, which plays an important functional role. proteolytic modifications may regulate its intracellular levels

AA Sequence

MTSFSTSAQCSTSDSACRISPGQINQVRPKLPLLKILHAAGAQGEMFTVKEVMHYLGQYIMVKQLYDQQE      1 - 70
QHMVYCGGDLLGELLGRQSFSVKDPSPLYDMLRKNLVTLATATTDAAQTLALAQDHSMDIPSQDQLKQSA     71 - 140
EESSTSRKRTTEDDIPTLPTSEHKCIHSREDEDLIENLAQDETSRLDLGFEEWDVAGLPWWFLGNLRSNY    141 - 210
TPRSNGSTDLQTNQDVGTAIVSDTTDDLWFLNESVSEQLGVGIKVEAADTEQTSEEVGKVSDKKVIEVGK    211 - 280
NDDLEDSKSLSDDTDVEVTSEDEWQCTECKKFNSPSKRYCFRCWALRKDWYSDCSKLTHSLSTSDITAIP    281 - 350
EKENEGNDVPDCRRTISAPVVRPKDAYIKKENSKLFDPCNSVEFLDLAHSSESQETISSMGEQLDNLSEQ    351 - 420
RTDTENMEDCQNLLKPCSLCEKRPRDGNIIHGRTGHLVTCFHCARRLKKAGASCPICKKEIQLVIKVFIA    421 - 490
//

Text Mined References (182)

PMID Year Title
27107012 2016 Pooled-matrix protein interaction screens using Barcode Fusion Genetics.
26471763 2015 MDM4 SNP34091 (rs4245739) and its effect on breast-, colon-, lung-, and prostate cancer risk.
26416355 2015 Opposite regulation of MDM2 and MDMX expression in acquisition of mesenchymal phenotype in benign and cancer cells.
26274820 2015 A Regulatory MDM4 Genetic Variant Locating in the Binding Sequence of Multiple MicroRNAs Contributes to Susceptibility of Small Cell Lung Cancer.
26181202 2015 Targeting Mdmx to treat breast cancers with wild-type p53.
26159518 2015 Assessing the Efficacy of Mdm2/Mdm4-Inhibiting Stapled Peptides Using Cellular Thermal Shift Assays.
26148237 2016 Structural basis of how stress-induced MDMX phosphorylation activates p53.
26028311 2015 MDM4 regulation by the let-7 miRNA family in the DNA damage response of glioma cells.
25961923 2016 MDM4/HIPK2/p53 cytoplasmic assembly uncovers coordinated repression of molecules with anti-apoptotic activity during early DNA damage response.
25825738 2015 Autoinhibition of MDMX by intramolecular p53 mimicry.
25809483 2015 The MDM2 RING domain and central acidic domain play distinct roles in MDM2 protein homodimerization and MDM2-MDMX protein heterodimerization.
25703327 2015 MDMX exerts its oncogenic activity via suppression of retinoblastoma protein.
25670033 2015 A genetic variant of MDM4 influences regulation by multiple microRNAs in prostate cancer.
25659040 2015 The alternative translated MDMX(p60) isoform regulates MDM2 activity.
25609649 2015 Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes.
25512388 2014 FL118 induces p53-dependent senescence in colorectal cancer cells by promoting degradation of MdmX.
25416956 2014 A proteome-scale map of the human interactome network.
25405759 2014 MDM4 overexpressed in acute myeloid leukemia patients with complex karyotype and wild-type TP53.
25394965 2014 [EEF1A2 inhibits the p53 function in hepatocellular carcinoma via PI3K/AKT/mTOR-dependent stabilization of MDM4].
25372739 2014 The MDM2 gene family.
25201988 2014 Common genetic variants associated with cognitive performance identified using the proxy-phenotype method.
25026175 2014 Copy number analysis of 24 oncogenes: MDM4 identified as a putative marker for low recurrence risk in non muscle invasive bladder cancer.
24972690 2014 Quantitative assessment of the association between HDMX polymorphism and sarcoma.
24755078 2014 A site-directed mutagenesis study of the MdmX RING domain.
24667108 2014 Amplification of Mdmx and overexpression of MDM2 contribute to mammary carcinogenesis by substituting for p53 mutations.
24659749 2014 High Mdm4 levels suppress p53 activity and enhance its half-life in acute myeloid leukaemia.
24608433 2015 Mdmx promotes genomic instability independent of p53 and Mdm2.
24488925 2014 The Mdm network and its regulation of p53 activities: a rheostat of cancer risk.
24445145 2014 Ubiquitin-specific protease 2a stabilizes MDM4 and facilitates the p53-mediated intrinsic apoptotic pathway in glioblastoma.
24325915 2014 Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer.
24285179 2014 EEF1A2 inactivates p53 by way of PI3K/AKT/mTOR-dependent stabilization of MDM4 in hepatocellular carcinoma.
24141721 2014 miR-661 downregulates both Mdm2 and Mdm4 to activate p53.
24127580 2013 MDMX contains an autoinhibitory sequence element.
24027430 2013 Stress-induced isoforms of MDM2 and MDM4 correlate with high-grade disease and an altered splicing network in pediatric rhabdomyosarcoma.
24018792 2013 In vitro and in silico studies of MDM2/MDMX isoforms predict Nutlin-3A sensitivity in well/de-differentiated liposarcomas.
23994448 2013 Identification and expression of a novel MDM4 splice variant in human glioma.
23946421 2013 Stapled ?-helical peptide drug development: a potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy.
23793604 2013 Functional MDM4 rs4245739 genetic variant, alone and in combination with P53 Arg72Pro polymorphism, contributes to breast cancer susceptibility.
23724042 2013 Association of a genetic variation in a miR-191 binding site in MDM4 with risk of esophageal squamous cell carcinoma.
23722424 2013 GWAS of 126,559 individuals identifies genetic variants associated with educational attainment.
23544013 2013 Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk.
23535733 2013 Genome-wide association studies identify four ER negative-specific breast cancer risk loci.
23535732 2013 Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
23324352 2013 On the interaction mechanisms of a p53 peptide and nutlin with the MDM2 and MDMX proteins: a Brownian dynamics study.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23028042 2012 Casein kinase 1? regulates an MDMX intramolecular interaction to stimulate p53 binding.
22937789 2012 S-MDM4 mRNA overexpression indicates a poor prognosis and marks a potential therapeutic target in chronic lymphocytic leukemia.
22916154 2012 Analysis of MDM2 and MDM4 single nucleotide polymorphisms, mRNA splicing and protein expression in retinoblastoma.
22870278 2012 MicroRNA-34a modulates MDM4 expression via a target site in the open reading frame.
22845047 2012 TP53 pathway analysis in paediatric Burkitt lymphoma reveals increased MDM4 expression as the only TP53 pathway abnormality detected in a subset of cases.
22825724 2012 Identification of a novel population in high-grade oligodendroglial tumors not deleted on 1p/19q using array CGH.
22820643 2012 MDM4 is a key therapeutic target in cutaneous melanoma.
22586610 2011 Discovery of Mdm2-MdmX E3 ligase inhibitors using a cell-based ubiquitination assay.
22556425 2012 Hypoxia activates tumor suppressor p53 by inducing ATR-Chk1 kinase cascade-mediated phosphorylation and consequent 14-3-3? inactivation of MDMX protein.
22493164 2012 Systematic analysis of dimeric E3-RING interactions reveals increased combinatorial complexity in human ubiquitination networks.
22490292 2012 [Correlation of polymorphism rs1563828 in MDM4 gene with breast cancer risk and onset age].
22410433 2012 Regulation of p53: a collaboration between Mdm2 and Mdmx.
22408446 2012 Computational studies of difference in binding modes of peptide and non-peptide inhibitors to MDM2/MDMX based on molecular dynamics simulations.
22374672 2012 MDM4 enhances p53 stability by promoting an active conformation of the protein upon DNA damage.
22333590 2012 Mutational analysis of Mdm2 C-terminal tail suggests an evolutionarily conserved role of its length in Mdm2 activity toward p53 and indicates structural differences between Mdm2 homodimers and Mdm2/MdmX heterodimers.
22290440 2012 MdmX is required for p53 interaction with and full induction of the Mdm2 promoter after cellular stress.
22180099 2012 Influence of MDM2 and MDM4 on development and survival in hereditary retinoblastoma.
22120712 2012 Abnormal MDMX degradation in tumor cells due to ARF deficiency.
22040960 2011 [mRNA levels detected by real-time quantitative RT-PCR in chronic lymphocytic leukemia and their clinical significance].
21988832 2011 Toward an understanding of the protein interaction network of the human liver.
21910853 2011 Oncogenic functions of hMDMX in in vitro transformation of primary human fibroblasts and embryonic retinoblasts.
21823114 2012 Modifying effect of MDM4 variants on risk of HPV16-associated squamous cell carcinoma of oropharynx.
21784052 2011 miR-10a overexpression is associated with NPM1 mutations and MDM4 downregulation in intermediate-risk acute myeloid leukemia.
21750655 2011 A small-molecule p53 activator induces apoptosis through inhibiting MDMX expression in breast cancer cells.
21572037 2011 MdmX protein is essential for Mdm2 protein-mediated p53 polyubiquitination.
21541195 2011 Functions of MDMX in the modulation of the p53-response.
21540763 2011 Polymorphisms of MDM4 and risk of squamous cell carcinoma of the head and neck.
21503588 2011 Rare MDM4 gene amplification in colorectal cancer: The principle of a mutually exclusive relationship between MDM alteration and TP53 inactivation is not applicable.
21148311 2011 14-3-3Gamma inhibition of MDMX-mediated p21 turnover independent of p53.
21088494 2010 Interaction of regulators Mdm2 and Mdmx with transcription factors p53, p63 and p73.
21084273 2010 An illegitimate microRNA target site within the 3' UTR of MDM4 affects ovarian cancer progression and chemosensitivity.
21081495 2011 c-Abl phosphorylation of Mdm2 facilitates Mdm2-Mdmx complex formation.
20863813 2010 MDM4 overexpression contributes to synoviocyte proliferation in patients with rheumatoid arthritis.
20855462 2010 Single-nucleotide polymorphisms in p53 pathway and aggressiveness of prostate cancer in a Caucasian population.
20819778 2010 MicroRNA-related genetic variations as predictors for risk of second primary tumor and/or recurrence in patients with early-stage head and neck cancer.
20810912 2010 Hypoxia downregulates p53 but induces apoptosis and enhances expression of BAD in cultures of human syncytiotrophoblasts.
20724842 2010 HdmX overexpression inhibits oncogene induced cellular senescence.
20713061 2010 Further insight into substrate recognition by USP7: structural and biochemical analysis of the HdmX and Hdm2 interactions with USP7.
20705607 2010 Turning the RING domain protein MdmX into an active ubiquitin-protein ligase.
20680659 2012 Histone deacetylase inhibitors enhance the anticancer activity of nutlin-3 and induce p53 hyperacetylation and downregulation of MDM2 and MDM4 gene expression.
20677014 2010 An approach based on a genome-wide association study reveals candidate loci for narcolepsy.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20520810 2010 Effects of MDM2, MDM4 and TP53 codon 72 polymorphisms on cancer risk in a cohort study of carriers of TP53 germline mutations.
20515689 2010 MDM4 binds ligands via a mechanism in which disordered regions become structured.
20472715 2010 HDMX regulates p53 activity and confers chemoresistance to 3-bis(2-chloroethyl)-1-nitrosourea.
20417304 2010 Puzzling over MDM4-p53 network.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20372076 2010 p53 inactivation by MDM2 and MDMX negative feedback loops in testicular germ cell tumors.
20333547 2011 Interplay between MDM2, MDMX, Pirh2 and COP1: the negative regulators of p53.
20190571 2010 Differential binding of p53 and nutlin to MDM2 and MDMX: computational studies.
20172729 2010 The p53 orchestra: Mdm2 and Mdmx set the tone.
20062013 2010 HDM4 is overexpressed in mantle cell lymphoma and its inhibition induces p21 expression and apoptosis.
19946469 2009 Alterations in gene expression and sensitivity to genotoxic stress following HdmX or Hdm2 knockdown in human tumor cells harboring wild-type p53.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19838211 2010 MdmX is a substrate for the deubiquitinating enzyme USP2a.
19762336 2009 A polymorphic variant in human MDM4 associates with accelerated age of onset of estrogen receptor negative breast cancer.
19734545 2009 A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB.
19721810 2009 MDM4 (MDMX) and its Transcript Variants.
19619542 2009 Mdmx enhances p53 ubiquitination by altering the substrate preference of the Mdm2 ubiquitin ligase.
19580521 2009 Stochastic modeling and simulation of the p53-MDM2/MDMX loop.
19521340 2009 MDM4 (MDMX) localizes at the mitochondria and facilitates the p53-mediated intrinsic-apoptotic pathway.
19507240 2009 Targeting the conformational transitions of MDM2 and MDMX: insights into key residues affecting p53 recognition.
19497887 2009 Altered tumor formation and evolutionary selection of genetic variants in the human MDM4 oncogene.
19470478 2009 Single-nucleotide polymorphisms in the p53 pathway regulate fertility in humans.
19305137 2009 High affinity interaction of the p53 peptide-analogue with human Mdm2 and Mdmx.
19273224 2009 MDM2 and MDM4 splicing: an integral part of the cancer spliceome.
19255450 2009 Structural basis for high-affinity peptide inhibition of p53 interactions with MDM2 and MDMX.
19153082 2009 Crystal Structures of Human MdmX (HdmX) in Complex with p53 Peptide Analogues Reveal Surprising Conformational Changes.
19084022 2009 Structure of human MDM4 N-terminal domain bound to a single-domain antibody.
19075013 2009 c-Abl phosphorylates Hdmx and regulates its interaction with p53.
18826207 2008 Targeting the conformational transitions of MDM2 and MDMX: insights into dissimilarities and similarities of p53 recognition.
18785023 2008 Genomic differences between retinoma and retinoblastoma.
18677113 2008 Structure of the human Mdmx protein bound to the p53 tumor suppressor transactivation domain.
18644346 2008 Expression of p14ARF, MDM2, and MDM4 in human retinoblastoma.
18566590 2008 The tumour suppressor RASSF1A promotes MDM2 self-ubiquitination by disrupting the MDM2-DAXX-HAUSP complex.
18451213 2008 High-resolution array-based comparative genomic hybridization of bladder cancers identifies mouse double minute 4 (MDM4) as an amplification target exclusive of MDM2 and TP53.
18356162 2008 Phosphorylation of MDMX mediated by Akt leads to stabilization and induces 14-3-3 binding.
18335186 2008 Analysis of human MDM4 variants in papillary thyroid carcinomas reveals new potential markers of cancer properties.
18279506 2008 Mutation analysis of the MDM4 gene in German breast cancer patients.
18172009 2008 Regulation of MDMX expression by mitogenic signaling.
18086887 2008 MDMX promotes proteasomal turnover of p21 at G1 and early S phases independently of, but in cooperation with, MDM2.
17875722 2007 Efficient p53 activation and apoptosis by simultaneous disruption of binding to MDM2 and MDMX.
17651783 2007 High levels of the p53 inhibitor MDM4 in head and neck squamous carcinomas.
17616658 2007 RING domain-mediated interaction is a requirement for MDM2's E3 ligase activity.
17159902 2007 An essential function of the extreme C-terminus of MDM2 can be provided by MDMX.
17110929 2006 MDMX regulation of p53 response to ribosomal stress.
17080083 2006 Inactivation of the p53 pathway in retinoblastoma.
17018606 2006 Genotoxic stress induces coordinately regulated alternative splicing of the p53 modulators MDM2 and MDM4.
16943424 2006 Differential roles of ATM- and Chk2-mediated phosphorylations of Hdmx in response to DNA damage.
16710414 2006 The DNA sequence and biological annotation of human chromosome 1.
16616333 2006 A mouse p53 mutant lacking the proline-rich domain rescues Mdm4 deficiency and provides insight into the Mdm2-Mdm4-p53 regulatory network.
16511572 2006 14-3-3gamma binds to MDMX that is phosphorylated by UV-activated Chk1, resulting in p53 activation.
16511560 2006 Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3.
16510145 2006 Effects of MdmX on Mdm2-mediated downregulation of pRB.
16266988 2005 Identification of an aberrantly spliced form of HDMX in human tumors: a new mechanism for HDM2 stabilization.
16227609 2005 DNA damage-induced phosphorylation of MdmX at serine 367 activates p53 by targeting MdmX for Mdm2-dependent degradation.
16163388 2005 ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage.
16082221 2005 ATM-mediated phosphorylations inhibit Mdmx/Mdm2 stabilization by HAUSP in favor of p53 activation.
16027727 2005 Rescue of Mdm4-deficient mice by Mdm2 reveals functional overlap of Mdm2 and Mdm4 in development.
15944197 2005 A functional polymorphism within the MRP1 gene locus identified through its genomic signature of positive selection.
15916963 2005 Loss of HAUSP-mediated deubiquitination contributes to DNA damage-induced destabilization of Hdmx and Hdm2.
15907800 2005 Modification of MDMX by sumoylation.
15906355 2005 Significance of HDMX-S (or MDM4) mRNA splice variant overexpression and HDMX gene amplification on primary soft tissue sarcoma prognosis.
15876864 2005 MdmX inhibits ARF mediated Mdm2 sumoylation.
15788536 2005 Phosphorylation of Hdmx mediates its Hdm2- and ATM-dependent degradation in response to DNA damage.
15782125 2005 Mdm2 and mdmX prevent ASPP1 and ASPP2 from stimulating p53 without targeting p53 for degradation.
15604276 2004 Adenoviral E1A targets Mdm4 to stabilize tumor suppressor p53.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15342556 2004 Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.
15199139 2004 Amplification of Mdmx (or Mdm4) directly contributes to tumor formation by inhibiting p53 tumor suppressor activity.
14739777 2004 MdmX represses E2F1 transactivation.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14660608 2004 MDM4 (MDMX) overexpression enhances stabilization of stress-induced p53 and promotes apoptosis.
12963717 2003 DNA damage-induced MDMX degradation is mediated by MDM2.
12860999 2003 MDM2 promotes ubiquitination and degradation of MDMX.
12761890 2003 Identification of a domain within MDMX-S that is responsible for its high affinity interaction with p53 and high-level expression in mammalian cells.
12640683 2003 Refined mapping of 1q32 amplicons in malignant gliomas confirms MDM4 as the main amplification target.
12532331 2003 The E2F-1 transcription factor is negatively regulated by its interaction with the MDMX protein.
12483531 2002 MdmX inhibits Smad transactivation.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12393902 2002 MdmX is a RING finger ubiquitin ligase capable of synergistically enhancing Mdm2 ubiquitination.
12370303 2002 DNA damage induces MDMX nuclear translocation by p53-dependent and -independent mechanisms.
12162806 2002 MDMX inhibits the p300/CBP-mediated acetylation of p53.
12107410 2002 Expressed sequence tag analysis of human RPE/choroid for the NEIBank Project: over 6000 non-redundant transcripts, novel genes and splice variants.
12101245 2002 Mdm4 (Mdmx) regulates p53-induced growth arrest and neuronal cell death during early embryonic mouse development.
11953423 2002 Mutual dependence of MDM2 and MDMX in their functional inactivation of p53.
11840567 2002 Cluster analysis of an extensive human breast cancer cell line protein expression map database.
11840332 2002 MDMX stability is regulated by p53-induced caspase cleavage in NIH3T3 mouse fibroblasts.
11528400 2001 Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a nonoverlapping pathway with MDM2 to regulate p53.
11297540 2001 MdmX binding to ARF affects Mdm2 protein stability and p53 transactivation.
10608892 1999 Stabilization of the MDM2 oncoprotein by interaction with the structurally related MDMX protein.
10469568 1999 MDM2 and MDMX bind and stabilize the p53-related protein p73.
10218570 1999 MDM2 interacts with MDMX through their RING finger domains.
10075736 1999 A novel MDMX transcript expressed in a variety of transformed cell lines encodes a truncated protein with potent p53 repressive activity.
9226370 1997 Isolation and identification of the human homolog of a new p53-binding protein, Mdmx.
8895579 1996 MDMX: a novel p53-binding protein with some functional properties of MDM2.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.