Recombinant Human Protein Mdm4 (MDM4)

1. Considering the lack of association between MDM4 rs4245739 polymorphism and breast cancer, rs4245739 polymorphism of this gene seems to have no significant role in the pathophysiology of the disease. PMID: 28164646
2. We conclude that Mdm4-S overexpression is a consequence of splicing defects in tumor cells rather than a cause of tumor evolution. PMID: 28460439
3. These results indicate that the rs4245739 polymorphism may contribute to a decreased cancer susceptibility and support the hypothesis that genetic variants in the MDM4 genes act as important modifiers of cancer risk. PMID: 27738340
4. our study is the first to identify miR-766 as a novel p53 activator that functions by targeting MDM4 and thereby enhancing the p53 signalling axis. PMID: 28430625
5. High MDM4 expression levels are associated with lymph node metastasis of gastric adenocarcinoma and influence the prognosis of patients with gastric adenocarcinoma PMID: 27626496
6. MDM4 rs4245739 A > C polymorphism appears to be associated with decreased cancer risk PMID: 27687591
7. analyses indicated that rs4245739 polymorphism in the MDM4 gene may play an important role in the etiology of cancer PMID: 27742919
8. results revealed an allosteric ligand-binding mechanism of the N-terminal domain of MdmX in which the ligand initially interacts with a compact core, followed by augmenting intermolecular interactions with intrinsic flexible regions PMID: 29023092
9. Complex alterations of HDM4 proteins, which are critical regulators of cell cycle progression, are frequent defects in AML and HG-MDS cases. The overall rates of detection of HDM4 expression in the present study, 92% in AML and 52% in MDS, respectively, indicate that HDM4 is a potential therapeutic target in patients with these diseases. PMID: 27155969
10. MDM4 rs1380576 G variant is associated with gastric cancer. PMID: 28099948
11. These results demonstrate that cisplatin-mediated p53(V172F) mutation regulates p53 stability at the normothermic temperature, but it is the increased recruitment of MDM4 by the homomeric or heteromeric mutant p53(V172F) complex that inhibits p53-dependent transactivation. This represents a novel cellular mechanism of p53 inhibition, and, thereby, induction of cisplatin resistance PMID: 26876197
12. MDM4 protein is frequently abundant in the context of mutant p53 in basal-like breast cancer (BC) samples. MDM4 plays a critical role in the proliferation of these BC cells. MDM4 is crucial for the establishment and progression of tumours. PMID: 28097652
13. Study used polymer statistics to estimate a global KD value for p53 binding to MdmX in the presence of the flexible linker and the intramolecular binding motif by assuming the flexible linker behaves as a wormlike chain. Calculations and measurements showed that the intramolecular binding motif reduces the apparent affinity of p53 for MdmX by a factor of 400. PMID: 28487147
14. Data indicate that knockdown of otubain 1 protein (Otub1) reduced the levels of double minute 4 protein (MDMX). PMID: 28035068
15. these data identify MDM4 as a nutrient-sensor able to inhibit mTORC1 and highlight its metabolism-related tumor-suppressing function. PMID: 28270148
16. Data indicate that two single-nucleotide polymorphism (SNPs)rs10900598 and rs4245739, located at 3'-untranslated region (UTR) of double minute 4 protein (MDM4) gene, contribute to clinical outcome of advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. PMID: 27462918
17. identified a novel Her4-induced posttranslational modification on MDMX PMID: 27777309
18. MDM4 SNP34091 polymorphism may function as a protective factor against cancer risk. PMID: 27646776
19. Individuals harboring the MDM4 SNP34091AC/CC genotypes had a significantly elevated risk for serous ovarian cancer, particularly high-grade serous ovarian cancer. No association between SNP34091 genotypes and endometrial cancer risk was observed. PMID: 26867771
20. These results suggest that secondary intermolecular interaction is important in p53 regulation by MDMX, which may represent a common phenomenon in complexes containing multidomain proteins. PMID: 27114532
21. 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. PMID: 26416355
22. 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. PMID: 26471763
23. 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. PMID: 26148237
24. MDM4/HIPK2/p53 cytoplasmic assembly uncovers coordinated repression of molecules with anti-apoptotic activity during early DNA damage response. PMID: 25961923
25. 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. PMID: 26274820
26. 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 PMID: 26181202
27. 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. PMID: 25405759
28. MDMX exerts oncogenic activity via suppression of RB. PMID: 25703327
29. 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 PMID: 25670033
30. 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 PMID: 26028311
31. 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. PMID: 25394965
32. Confirmation that the residue Tyr99 in MDMX can generate a steric clash with the inhibitors due to energy and structure. PMID: 22408446
33. The HDMX polymorphism is unlikely to contribute to individual susceptibility to sarcoma. PMID: 24972690
34. The results indicate a putative role for the MDM4 gene in predicting local recurrence of bladder cancer. PMID: 25026175
35. Endogenously high levels of Mdm4 inhibit and sequester p53 in AML. High levels of Mdm4 do not block function of Mdm2 inhibitors in AML. PMID: 24659749
36. in the absence of p53 or in the presence of MdmX overexpression, FL118 promotes p53-independent apoptosis PMID: 25512388
37. Downregulation of Mdm4 by miR-661 augments p53 activity and inhibits cell cycle progression in p53-proficient cells. PMID: 24141721
38. Loss of MDM4 expression is associated with glioblastoma. PMID: 24445145
39. the novel variant MDM4-B may play a role in glioma tumorigenesis or cancer progression PMID: 23994448
40. The activation level of the EEF1A2/PI3K/AKT/mTOR/MDM4 axis significant influences the survival probability of hepatocellular carcinoma patients. PMID: 24285179
41. 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. PMID: 23793604
42. MDMX contains a regulatory element (the "WWW element") that binds to its own N-terminal domain and prevents MDMX from binding to p53. PMID: 24127580
43. The MDM4 rs4245739 (miR-191 target site) AC and CC genotypes were significantly associated with decreased esophageal squamous cell carcinoma risk PMID: 23724042
44. 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. PMID: 22820643
45. 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. PMID: 23324352
46. 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. PMID: 22490292
47. 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. PMID: 22937789
48. MicroRNA-34a modulates MDM4 expression via a target site in the open reading frame. PMID: 22870278
49. The results of this study showed that strong association between MDM4 gene alternation and high-grade oligodendroglial tumors. PMID: 22825724
50. DNA damage activates p53 in part by disrupting CK1a-MDMX interaction and reducing MDMX-p53 binding affinity. PMID: 23028042

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HGNC: 6974

OMIM: 602704

KEGG: hsa:4194

STRING: 9606.ENSP00000356150

UniGene: Hs.497492