High impact information on Mdm2

• Expression of a p53-associated protein, Mdm-2 (murine double minute-2), can inhibit p53-mediated transactivation [1].
• In this study, overexpression of the Mdm-2 protein was found to result in the immortalization of primary rat embryo fibroblasts (REFs) and, in conjunction with an activated ras gene, in the transformation of REFs [1].
• A low level of Mdm2 in nuclei was observed in surrounding liver, while both Mdm2 and Bcl-2 protein were strongly expressed in the cytoplasm in foci [2].
• X-ray exposure further induced nuclear expression of p53, p21(waf1/cip1), and Mdm2 in surrounding hepatocytes, but focal nuclei were still negative [2].
• Transforming growth factor beta1 (TGF-beta1)-induced hepatocyte apoptosis is associated with activation of E2F transcription factors and p53 stabilization through Mdm-2, thus potentially modulating a number of target genes [3].

Biological context of Mdm2

• Loss of nuclear p53 protein in preneoplastic rat hepatocytes is accompanied by Mdm2 and Bcl-2 overexpression and by defective response to DNA damage in vivo [2].
• Insulin-like growth factor-1 induces Mdm2 and down-regulates p53, attenuating the myocyte renin-angiotensin system and stretch-mediated apoptosis [4].
• The effects of IGF-1 on cell death, Ang II synthesis, and Bax protein were the consequence of Mdm2-induced down-regulation of p53 function [4].
• The negative regulator of p53 transactivation, Mdm2, increased in the ischemic territory after 90 minutes of transient middle cerebral artery occlusion in spontaneously hypertensive rats compared to sham controls [5].
• Here we demonstrate that following a preconditioning protocol, the proapoptotic p53 is inactivated possibly via phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-murine double minute 2 (Mdm2) phosphorylation [6].

Anatomical context of Mdm2

• Increased Mdm2 expression in rat brain after transient middle cerebral artery occlusion [5].
• A significant increase in nuclear Mdm2 immunoreactivity, which colocalized with p53, was observed in cells within hippocampal pyramidal cell layers, dentate gyrus, piriform cortex, amygdala and thalamus [7].

Associations of Mdm2 with chemical compounds

• Here we demonstrate increased expression and co-localization of p53 and Mdm2 in the nuclei of degenerating neurons following treatment with either the excitotoxin, kainic acid, or the topoisomerase I inhibitor, camptothecin [8].
• Further, the E2F-1/Mdm-2/p53 apoptotic pathway appears to be a prime target for UDCA-induced steroid receptor activation [9].
• In animals treated with dexmedetomidine, the expression of Bcl-2 and Mdm-2 was larger compared with control (68% and 210%, respectively) or sham-operated (110% and 180%, respectively) animals [10].

Physical interactions of Mdm2

• The addition of exogenous ubiquitin to p53-Mdm2 complexes from apoptotic neurons restored p53 degradation [11].

Analytical, diagnostic and therapeutic context of Mdm2

• Immunohistochemical staining for Mdm2 revealed that its mRNA was efficiently translated in the ischemic cortex, but not striatum, by 8 to 24 hours of reperfusion [5].
• Our data show that in preconditioned hearts Mdm2 was significantly phosphorylated, and wortmannin (a PI3K inhibitor) abrogated this effect (Western blotting) [6].
• Co-immunoprecipitation studies showed that p53-Mdm2 complexes were present in neuronal lysates [8].
• Dual immunofluorescence microscopy revealed a reduction in free ubiquitin expression in cells with p53 and Mdm2 accumulation [7].
• We used immunohistochemistry to examine the expression of Mdm2, Bax, CD95/Fas/APO-1, ATM, Ref-1 and ubiquitin [7].

References