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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
Complex alterations of HDM4 proteins, which are critical regulators of cell cycle progression, are frequent defects in AML (zeige RUNX1 Proteine) and HG-MDS (zeige PAFAH1B1 Proteine) cases. The overall rates of detection of HDM4 expression in the present study, 92% in AML (zeige RUNX1 Proteine) and 52% in MDS (zeige PAFAH1B1 Proteine), respectively, indicate that HDM4 is a potential therapeutic target in patients with these diseases.
MDM4 rs1380576 G variant is associated with gastric cancer.
These results demonstrate that cisplatin-mediated p53 (zeige TP53 Proteine)(V172F) mutation regulates p53 (zeige TP53 Proteine) stability at the normothermic temperature, but it is the increased recruitment of MDM4 by the homomeric or heteromeric mutant p53 (zeige TP53 Proteine)(V172F) complex that inhibits p53 (zeige TP53 Proteine)-dependent transactivation. This represents a novel cellular mechanism of p53 (zeige TP53 Proteine) inhibition, and, thereby, induction of cisplatin resistance
MDM4 protein is frequently abundant in the context of mutant p53 (zeige TP53 Proteine) 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 (zeige TP53 Proteine) 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 (zeige TP53 Proteine) for MdmX by a factor of 400.
Data indicate that knockdown of otubain 1 (zeige OTUB1 Proteine) 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 (zeige MDM2 Proteine) splice isoforms may play critical roles in the regulatory loop of p53 (zeige TP53 Proteine)/Mdm2 (zeige MDM2 Proteine)-Mdm4 via a RING domain-mediated biochemical mechanism.
Data indicate that knockdown of the Mdm2 (zeige MDM2 Proteine) and Mdm4 caused dramatic accumulation of mutant p53 protein (zeige TP53 Proteine).
crystal structure of N-terminal domain of Mdmx bound to 15-residue p53 (zeige TP53 Proteine) peptide was determined; structure reveals that although principle features of Mdm2 (zeige MDM2 Proteine)-p53 (zeige TP53 Proteine) interaction are preserved, the Mdmx hydrophobic cleft on which the p53 (zeige TP53 Proteine) peptide binds is altered
The p53 (zeige TP53 Proteine)-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 (zeige MDM2 Proteine) and MDMX deletion-caused pancreatic defects are completely rescued by loss of p53 (zeige TP53 Proteine), verifying the crucial role of the MDM2 (zeige MDM2 Proteine) and/or MDMX in regulating p53 (zeige TP53 Proteine) 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 (zeige TP53 Proteine) level in mutant oocytes, nor any other apoptotic marker, introgression of this targeted invalidation in p53 (zeige TP53 Proteine)-/- mice restored the fertility of females. This study is the first to show that Mdm2 (zeige MDM2 Proteine), 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 (zeige ARHGAP24 Proteine) axis cannot override the dominant role of p53 (zeige TP53 Proteine) in development and tumorigenesis and that Mdm4 and p73 (zeige ARHGAP24 Proteine) interaction during development and tumorigenesis suggests new insight into the role of p53 (zeige TP53 Proteine) family members.
MDM4/HIPK2 (zeige HIPK2 Proteine)/p53 (zeige TP53 Proteine) 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 (zeige CASP3 Proteine) activation in neurons, and that the progressive loss of MDMx protein represents a potential mechanism of Abeta (zeige APP Proteine)-induced neuronal death during disease progression in AD
our results show MDM4-MDM2 (zeige MDM2 Proteine)/p53 (zeige TP53 Proteine)-IGF1R (zeige IGF1R Proteine) 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 (zeige TP53 Proteine)- and Mdm2 (zeige MDM2 Proteine)-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