|
ORF cDNA clones
|
CRISPR / TALEN
|
Lentivirus
|
AAV
|
TALE-TF
|
ORF knockin clones
|
|
Antibody
|
Proteins
|
miRNA target clones
|
qPCR primers
|
shRNA clones
|
miRNA products
|
Promoter clones
|
Validated All-in-One™ qPCR Primer for MDM4(NM_002393.4) Search again
Product ID:
HQP011140
(click here to view gene annotation page)
Powered by BiozSpecies:
Human
Symbol:
Alias:
BMFS6, HDMX, MDMX, MRP1
Gene Description:
MDM4 regulator of p53
Target Gene Accession:
NM_002393.4(click here to view gene page)
Estimated Delivery:
Approximately 1-3 weeks, but may vary. Please email sales@genecopoeia.com or call 301-762-0888 to confirm ETA.
Important Note:
By default, qPCR primer pairs are designed to measure the expression level of the splice variant (accession number) you selected for this gene WITHOUT consideration of other possible variants of this gene. If this gene has multiple variants, and you would like to measure the expression levels of one particular variant, multiple variants, or all variants, please contact us for a custom service project at inquiry@genecopoeia.com.
Validated result:
|
|
| A | B |
|
Each All-in-One™ qPCR Primer is experimentally validated to yield a single dissociation curve peak and to generate a single amplification of the correct size for the targeted gene. A cDNA Pool, containing reverse transcript products of 8 different human tissue total RNA(Liver, Testis,Muscle,Thyroid,Brain,Spleen,Stomach,Small Intestine)),was used as the qPCR validation template. qPCR was performed using 0.2 µM primer with 2XAll-in-One™ qPCR Mix (Catalog#: QP001,QP002,QP004,QP005). Reactions were incubated for 10min. at 95°C, followed by 40 cycles of 95°C for 10 sec.; 60°C, 20 sec. and 72°C, 15sec. using Bio-Rad iQ5™ Instrument. At the end of the last cycle, temperature was increased from 72 to 95°C to produce a melting curve. Panel A: Validated Result for Amplification Curve; Panel B: Validated Result for Melting Curve. |
|
Summary
The human MDM4 gene, which plays a role in apoptosis, encodes a 490-amino acid protein containing a RING finger domain and a putative nuclear localization signal. The MDM4 putative nuclear localization signal, which all Mdm proteins contain, is located in the C-terminal region of the protein. The mRNA is expressed at a high level in thymus and at lower levels in all other tissues tested. MDM4 protein produced by in vitro translation interacts with p53 via a binding domain located in the N-terminal region of the MDM4 protein. MDM4 shows significant structural similarity to p53-binding protein MDM2. Two transcript variants, one protein-coding and the other likely not to be protein-coding, have been found for this gene. [provided by RefSeq].
Gene References into function
- stability is regulated by p53-induced caspase cleavage, which plays an important functional role. proteolytic modifications may regulate its intracellular levels
- MDMX, when exceedingly overexpressed, inhibits MDM2-mediated p53 degradation by competing with MDM2 for p53 binding
- MDMX dramatically inhibits the acetylation of p53 induced by both endogenous and ectopically expressed p300/CBP.
- MDMX is transported to the cell nucleus upon DNA damage with or without p53
- MdmX is a RING finger ubiquitin ligase capable of synergistically enhancing Mdm2 ubiquitination
- Smad-induced transactivation by MdmX occurs by altering Smad interaction with its coactivator p300
- mouse double minute 4 homolog gene amplification is associated with malignant gliomas on 1q32
- MDMX is ubiquinated and degraded by MDM2
- DNA damage-induced MDMX degradation is mediated by MDM2
- 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
- MdmX represses E2F1 transactivation
- 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
- Mdm2 and mdmx prevent ASPP1 and ASPP2 from stimulating the apoptotic function of p53 by binding and inhibiting the transcriptional activity of p53.
- sites important for Hdm2-mediated ubiquitination of Hdmx after double-strand break induction
- MdmX can affect post-translational modification and stability of Mdm2 and p53 activity through interaction with ARF
- HDMX gene was amplified in 17% of soft tissue sarcoma patienets and gene amplification was associated with poor prognosis.
- 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
- 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
- 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
- ATM directly activates p53 while activating a safe-lock mechanism to inactivate the negative regulators of p53, Mdm2, and Mdmx [review]
- ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage.
- MdmX may have different roles in the regulation of Mdm2 activity for ubiquitination of pRB and p53
- Mdm4 regulates tumor suppressor p53 activity, while Mdm2 mainly controls p53 stability
- 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.
- 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.
- 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
- MDMX is an important regulator of p53 response to ribosomal stress and RNA-targeting chemotherapy agents.
- functions of the extreme C-terminus of MDM2 can be provided by MDMX
- the MDM2 and MDMX complex has a role in abundance and activity of p53
- 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.
- 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.
- 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.
- There is no evidence for a major role of MDM4 coding variants in the inherited susceptibility towards breast cancer in German patients.
- 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.
- 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
- 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.
- Overexpression of MDM2 and MDM4 is not a necessary step in retinoblastoma development.
- Structure of the human Mdmx protein bound to the p53 tumor suppressor transactivation domain.
- MDM4 gain is associated with the early transition from normal retina to retinoma.
- 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
- 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.