MDM2


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MDM2

Murine double minute-2. A gene that encodes a 90-kD nuclear phosphoprotein with a binding site for the tumour suppressor p53. Once a MDM2-p53 complex is formed, p53 activity is rapidly down-regulated and p53 is degraded by a ubiquitin-proteasome pathway. MDM2 inhibits p53 activity by inhibiting transfer of p53 from cytoplasm to nucleus, blocking p53-DNA interaction and, by ubiquitinising p53, inhibits apoptosis. These actions, coupled with CDK4 inhibition of RB1 by phosphorylation, release the G1-S checkpoint. MDM2 and CDK4 amplification occurs in a range of carcinomas and sarcomas—especially liposarcomas and haemopoietic neoplasia. MDM2 protein expression is a negative prognostic marker in breast carcinoma.
References in periodicals archive ?
Therefore, when facing a high-grade and pleomorphic sarcoma biopsy from the retroperitoneum, judicious use of immunohistochemical stains for MDM2 and CDK4 is helpful in identifying dedifferentiated liposarcoma.
Sun, "Discovery of a small molecule MDM2 inhibitor (AMG 232) for treating cancer," Journal of Medicinal Chemistry, vol.
Roessner, "Clinicopathologiclmplications of MDM2, p53 and K-ras gene alterations in osteosarcomas: MDM2 amplification and p53 mutations found in progressive tumors," Pathology--Research and Practice, vol.
In addition to approved medicines MabThera/Rituxan and Gazyva/Gazyvaro, Roche's pipeline of investigational hematology medicines includes an anti-CD79b antibody drug conjugate (RG7596/polatuzumab vedotin), a small molecule antagonist of MDM2 (RG7112) and in collaboration with AbbVie, a small molecule BCL-2 inhibitor (venetoclax/RG7601/GDC-0199/ABT-199).
In this study, a potential of mean force method was used to calculate the absolute binding affinities for the disordered p53 and MDM2 when the proline in p53 is in both cis and trans conformations.
Studies have shown that a Single Nucleotide Polymorphism (SNP) on promoter region of MDM2 gene, the SNP309 (T to G change on nucleotide 309 of the first intron), results in a higher level of MDM2 mRNA and MDM2 protein, and consequent reduction of the p53 pathway.
Krishna et al studied protein over expression (MDM2) in ameloblastoma and oral squamous cell carcinoma (OSCC) and found that the keratinizing cells of acanthomatous ameloblastoma showed less MDM2 reactivity as compared to high reactivity in OSCC which could be suggestive of terminal differentiation and non-proliferative phenotype of central cells.
To clarify this hypothesis, it is mentioned that Mdm2 (Mouse double minute 2 homolog) which has been recognized as E3 ubiquitin-protein ligase, regulates both the transcriptional activity and the half-life of p53 in a negative feedback loop.
2007), 3 case-control studies on the 309T> G polymorphism of MDM2 (Mouse double minute 2 homolog) gene (Sousa, Pando, Breda, Catarino, & Medeiros, 2011; Xiao et al.