Recombinant Human Protein Mdm4 (MDM4) Protein (His)

Name: Recombinant Human Protein Mdm4 (MDM4) Protein (His)
Brand: Beta LifeScience
SKU: BLC-01763P
Availability: InStock

Greater than 90% as determined by SDS-PAGE.

Collections: All products, High-quality recombinant proteins, Other recombinant proteins

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Product Overview

Description	Recombinant Human Protein Mdm4 (MDM4) Protein (His) is produced by our E.coli expression system. This is a full length protein.
Purity	Greater than 90% as determined by SDS-PAGE.
Uniprotkb	O15151
Target Symbol	MDM4
Synonyms	Double minute 4 protein Mdm2-like p53-binding protein Protein Mdmx p53-binding protein Mdm4
Species	Homo sapiens (Human)
Expression System	E.coli
Tag	N-6His
Target Protein Sequence	MTSFSTSAQCSTSDSACRISPGQINQVRPKLPLLKILHAAGAQGEMFTVKEVMHYLGQYIMVKQLYDQQEQHMVYCGGDLLGELLGRQSFSVKDPSPLYDMLRKNLVTLATATTDAAQTLALAQDHSMDIPSQDQLKQSAEESSTSRKRTTEDDIPTLPTSEHKCIHSREDEDLIENLAQDETSRLDLGFEEWDVAGLPWWFLGNLRSNYTPRSNGSTDLQTNQDVGTAIVSDTTDDLWFLNESVSEQLGVGIKVEAADTEQTSEEVGKVSDKKVIEVGKNDDLEDSKSLSDDTDVEVTSEDEWQCTECKKFNSPSKRYCFRCWALRKDWYSDCSKLTHSLSTSDITAIPEKENEGNDVPDCRRTISAPVVRPKDAYIKKENSKLFDPCNSVEFLDLAHSSESQETISSMGEQLDNLSEQRTDTENMEDCQNLLKPCSLCEKRPRDGNIIHGRTGHLVTCFHCARRLKKAGASCPICKKEIQLVIKVFIA
Expression Range	1-490aa
Protein Length	Full Length
Mol. Weight	59.0 kDa
Research Area	Cell Cycle
Form	Liquid or Lyophilized powder
Buffer	Liquid form: default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. Lyophilized powder form: the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution	Briefly centrifuged the vial prior to opening to bring the contents to the bottom. Reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. It is recommended to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. The default final concentration of glycerol is 50%.
Storage	1. Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. 2. Avoid repeated freeze-thaw cycles. 3. Store working aliquots at 4°C for up to one week. 4. In general, protein in liquid form is stable for up to 6 months at -20°C/-80°C. Protein in lyophilized powder form is stable for up to 12 months at -20°C/-80°C.
Notes	Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Target Details

Target Function	Along with MDM2, contributes to TP53 regulation. Inhibits p53/TP53- and TP73/p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions.
Subcellular Location	Nucleus.
Protein Families	MDM2/MDM4 family
Database References	HGNC: 6974 OMIM: 602704 KEGG: hsa:4194 STRING: 9606.ENSP00000356150 UniGene: PMID: 28164646 We conclude that Mdm4-S overexpression is a consequence of splicing defects in tumor cells rather than a cause of tumor evolution. PMID: 28460439 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 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 High MDM4 expression levels are associated with lymph node metastasis of gastric adenocarcinoma and influence the prognosis of patients with gastric adenocarcinoma PMID: 27626496 MDM4 rs4245739 A > C polymorphism appears to be associated with decreased cancer risk PMID: 27687591 analyses indicated that rs4245739 polymorphism in the MDM4 gene may play an important role in the etiology of cancer PMID: 27742919 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 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 MDM4 rs1380576 G variant is associated with gastric cancer. PMID: 28099948 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 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 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 Data indicate that knockdown of otubain 1 protein (Otub1) reduced the levels of double minute 4 protein (MDMX). PMID: 28035068 these data identify MDM4 as a nutrient-sensor able to inhibit mTORC1 and highlight its metabolism-related tumor-suppressing function. PMID: 28270148 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 identified a novel Her4-induced posttranslational modification on MDMX PMID: 27777309 MDM4 SNP34091 polymorphism may function as a protective factor against cancer risk. PMID: 27646776 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 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 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 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 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 MDM4/HIPK2/p53 cytoplasmic assembly uncovers coordinated repression of molecules with anti-apoptotic activity during early DNA damage response. PMID: 25961923 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 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 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 MDMX exerts oncogenic activity via suppression of RB. PMID: 25703327 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 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 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 Confirmation that the residue Tyr99 in MDMX can generate a steric clash with the inhibitors due to energy and structure. PMID: 22408446 The HDMX polymorphism is unlikely to contribute to individual susceptibility to sarcoma. PMID: 24972690 The results indicate a putative role for the MDM4 gene in predicting local recurrence of bladder cancer. PMID: 25026175 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 in the absence of p53 or in the presence of MdmX overexpression, FL118 promotes p53-independent apoptosis PMID: 25512388 Downregulation of Mdm4 by miR-661 augments p53 activity and inhibits cell cycle progression in p53-proficient cells. PMID: 24141721 Loss of MDM4 expression is associated with glioblastoma. PMID: 24445145 the novel variant MDM4-B may play a role in glioma tumorigenesis or cancer progression PMID: 23994448 The activation level of the EEF1A2/PI3K/AKT/mTOR/MDM4 axis significant influences the survival probability of hepatocellular carcinoma patients. PMID: 24285179 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 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 The MDM4 rs4245739 (miR-191 target site) AC and CC genotypes were significantly associated with decreased esophageal squamous cell carcinoma risk PMID: 23724042 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 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 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 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 MicroRNA-34a modulates MDM4 expression via a target site in the open reading frame. PMID: 22870278 The results of this study showed that strong association between MDM4 gene alternation and high-grade oligodendroglial tumors. PMID: 22825724 DNA damage activates p53 in part by disrupting CK1a-MDMX interaction and reducing MDMX-p53 binding affinity. PMID: 23028042

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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