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MDM4 rs1380576 G variant is associated with gastric cancer.
These results demonstrate that cisplatin-mediated p53 (show TP53 Proteins)(V172F) mutation regulates p53 (show TP53 Proteins) stability at the normothermic temperature, but it is the increased recruitment of MDM4 by the homomeric or heteromeric mutant p53 (show TP53 Proteins)(V172F) complex that inhibits p53 (show TP53 Proteins)-dependent transactivation. This represents a novel cellular mechanism of p53 (show TP53 Proteins) inhibition, and, thereby, induction of cisplatin resistance
MDM4 protein is frequently abundant in the context of mutant p53 (show TP53 Proteins) 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.
Study used polymer statistics to estimate a global KD value for p53 (show TP53 Proteins) 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 (show TP53 Proteins) for MdmX by a factor of 400.
Data indicate that knockdown of otubain 1 (show OTUB1 Proteins) protein (Otub1) reduced the levels of double minute 4 protein (MDMX).
these data identify MDM4 as a nutrient-sensor able to inhibit mTORC1 and highlight its metabolism-related tumor-suppressing function.
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.
These findings suggest that Mdm2 (show MDM2 Proteins) splice isoforms may play critical roles in the regulatory loop of p53 (show TP53 Proteins)/Mdm2 (show MDM2 Proteins)-Mdm4 via a RING domain-mediated biochemical mechanism.
AXL (show AXL Proteins) overexpression or activation through growth arrest-specific 6 (Gas6 (show GAS6 Proteins)) ligand stimulation increases MDMX and MDM2 (show MDM2 Proteins) protein levels and decreases p53 (show TP53 Proteins) activity.
p53 (show TP53 Proteins) stabilization, along with antagonism of its signaling partners, MDM2 (show MDM2 Proteins) and MDMX, is a promising strategy for anticancer targeted therapy. (Review)
Data indicate that knockdown of the Mdm2 (show MDM2 Proteins) and Mdm4 caused dramatic accumulation of mutant p53 protein (show TP53 Proteins).
crystal structure of N-terminal domain of Mdmx bound to 15-residue p53 (show TP53 Proteins) peptide was determined; structure reveals that although principle features of Mdm2 (show MDM2 Proteins)-p53 (show TP53 Proteins) interaction are preserved, the Mdmx hydrophobic cleft on which the p53 (show TP53 Proteins) peptide binds is altered
The p53 (show TP53 Proteins)-null mice with the highest level of Mdm4 tended to have multiple tumours. Mdm4 transgenic mice in various genetic backgrounds shows synergy in tumour development in vivo. Mdm4 may thus serve as a therapeutic target in cancers.
both MDM2 (show MDM2 Proteins) and MDMX deletion-caused pancreatic defects are completely rescued by loss of p53 (show TP53 Proteins), verifying the crucial role of the MDM2 (show MDM2 Proteins) and/or MDMX in regulating p53 (show TP53 Proteins) in a spatio-temporal manner during the development, functional maintenance, and related disease progress of endocrine pancreas.
we failed to detect any increase in p53 (show TP53 Proteins) level in mutant oocytes, nor any other apoptotic marker, introgression of this targeted invalidation in p53 (show TP53 Proteins)-/- mice restored the fertility of females. This study is the first to show that Mdm2 (show MDM2 Proteins), but not Mdm4, has a critical role in oocyte survival and would be involved in premature ovarian insufficiency phenotype.
Data show that the Mdm4-p73 (show ARHGAP24 Proteins) axis cannot override the dominant role of p53 (show TP53 Proteins) in development and tumorigenesis and that Mdm4 and p73 (show ARHGAP24 Proteins) interaction during development and tumorigenesis suggests new insight into the role of p53 (show TP53 Proteins) family members.
MDM4/HIPK2 (show HIPK2 Proteins)/p53 (show TP53 Proteins) cytoplasmic assembly uncovers coordinated repression of molecules with anti-apoptotic activity during early DNA damage response.
MDMx degradation associated with neuronal death occurs via caspase (show CASP3 Proteins) activation in neurons, and that the progressive loss of MDMx protein represents a potential mechanism of Abeta (show APP Proteins)-induced neuronal death during disease progression in AD
our results show MDM4-MDM2 (show MDM2 Proteins)/p53 (show TP53 Proteins)-IGF1R (show IGF1R Proteins) as an original regulatory mechanism for CNS regeneration
Increased Mdm4-S mRNA levels might correlate with more aggressive cancers without encoding significant amounts of a potential oncoprotein.
results reveal a novel p53 (show TP53 Proteins)- and Mdm2 (show MDM2 Proteins)-independent oncogenic function of Mdmx that provides new insight into the many cancers that overexpress Mdmx.
This gene encodes a nuclear protein that contains a p53 binding domain at the N-terminus and a RING finger domain at the C-terminus, and shows structural similarity to p53-binding protein MDM2. Both proteins bind the p53 tumor suppressor protein and inhibit its activity, and have been shown to be overexpressed in a variety of human cancers. However, unlike MDM2 which degrades p53, this protein inhibits p53 by binding its transcriptional activation domain. This protein also interacts with MDM2 protein via the RING finger domain, and inhibits the latter's degradation. So this protein can reverse MDM2-targeted degradation of p53, while maintaining suppression of p53 transactivation and apoptotic functions. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.
double minute 4 protein
, mdm2-like p53-binding protein
, p53-binding protein Mdm4
, protein Mdm4
, MDM4-related protein 1
, double minute 4, human homolog of; p53-binding protein
, protein Mdmx
, Mdm4, transformed 3T3 cell double minute 4, p53 binding protein
, double minute 4 homolog
, transformed mouse 3T3 cell double minute 4