Mdmx: A p53 activator?
نویسندگان
چکیده
منابع مشابه
Autoinhibition of MDMX by intramolecular p53 mimicry.
The p53 inhibitor MDMX is controlled by multiple stress signaling pathways. Using a proteolytic fragment release (PFR) assay, we detected an intramolecular interaction in MDMX that mechanistically mimics the interaction with p53, resulting in autoinhibition of MDMX. This mimicry is mediated by a hydrophobic peptide located in a long disordered central segment of MDMX that has sequence similarit...
متن کاملControlling the Mdm2-Mdmx-p53 Circuit
The p53 tumor suppressor is a key protein in maintaining the integrity of the genome by inducing either cell cycle arrest or apoptosis following cellular stress signals. Two human family members, Mdm2 and Mdmx, are primarily responsible for inactivating p53 transcription and targeting p53 protein for ubiquitin-mediated degradation. In response to genotoxic stress, post-translational modificatio...
متن کاملRegulation of p53: a collaboration between Mdm2 and MdmX
p53 plays an important role in the regulation of the cell cycle, DNA repair, and apoptosis and is an attractive cancer therapeutic target. Mdm2 and Mdmx are recognized as the main p53 negative regulators. Although it remains unclear why Mdm2 and Mdmx are both required for p53 degradation, a model has been proposed whereby these two proteins function independent of one another; Mdm2 acts as an E...
متن کاملmdmx is a negative regulator of p53 activity in vivo.
Regulation of p53 protein activity is required for normal embryogenesis, tumor suppression, and cellular response to DNA damage. Here we report that loss of mdmx, a p53-binding protein, results in midgestational embryo lethality, a phenotype that is completely rescued by the absence of p53. Mice homozygous for both mdmx and p53 null mutations are viable and appear developmentally normal. Fibrob...
متن کاملMdmX protein is essential for Mdm2 protein-mediated p53 polyubiquitination.
Genetic evidence has implicated both Mdm2 and MdmX as essential in negative regulation of p53. However, the exact role of MdmX in this Mdm2-dependent protein degradation is not well understood. Most, if not all, previous Mdm2 studies used GST-Mdm2 fusion proteins in the in vitro assays. Here, we show that the p53 polyubiquitination activity of GST-Mdm2 is conferred by the GST tag and non-GST-ta...
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ژورنال
عنوان ژورنال: Cell Cycle
سال: 2012
ISSN: 1538-4101,1551-4005
DOI: 10.4161/cc.11.5.19597