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 ?
The p53 and MDM2 proteins function in the same cell proliferation pathway and have directly antagonistic functions.
The Mdm2 inhibitor, NVP-CGM097, in combination with the BRAF inhibitor NVP-LGX818 elicits synergistic antitumor effects in melanoma (Abstract #5466; April 9, 8:00 a.
In addition, HMGA2 has been shown to be the target gene in pleomorphic adenoma with translocations involving 12q14-15 and is frequently coamplified with MDM2.
Nuclear export is required for degradation of endogenous p53 by MDM2 and human papillomavirus E6.
75 and round cell) EWS-CHOP Rare EWS-CHOP Rare Atypical lipomatous HMGIC, CDK4, and Most tumor, MDM2 amplification well-differentiated liposarcoma Lipoblastoma HAS2-PLAG1, Most COL1A2-PLAG1 Clear cell sarcoma EWS-ATF1 .
254,352) Nutlin-3a, an MDM2 inhibitor, has shown apoptotic activity in ALK+ ALCL cell lines through reactivation of p53 or possibly other tumor suppressors such as p73.
MDM2 FISH has been used only very recently at our institution due to the recent development of a MDM2 gene region probe (n = 20) (Table 2).
Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain.
A decrease in mdm2 expression has been seen in tumors with adverse histologic features.
An overabundance of MDMX or its sister protein, MDM2, can promote tumor progression by binding and suppressing a protein called p53.
With AT-101, an oral, pan-Bcl-2 inhibitor compound in multiple Phase 2 clinical trials in both solid and heme tumors and a preclinical pipeline of compounds directed against MDM2 and XIAP, two key apoptosis targets, Ascenta is focused on developing a broad portfolio of apoptotic therapeutics for the treatment of cancer.
Ascenta's MDM2 program has been selected for presentation at the "High Impact Late-Breaking Research 1" session on Tuesday, April 17 (Hall A at 3:30pm) and will be presented by Dajun Yang, MD, PhD, Senior Vice President of Research at Ascenta Therapeutics and General Manager of Ascenta's R&D Subsidiary in Shanghai, China.