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 ?
Furthermore, oridonin reduced the protein expression of Mdm2. Mdm2, widely proven to be a negative regulator of p53, represses p53 transcriptional activity and mediates the degradation of p53 (32,33).
In tumors where a well-differentiated component is not identified, however, DL can still be diagnosed by the detection of MDM2 amplification via fluorescence in situ hybridization (FISH) or real-time polymerase chain reaction, (2,3,20) which is also true for myofibroblastic DL.
"Well-Differentiated Laryngeal/Hypopharyngeal Liposarcoma in the MDM2 Era Report of Three Cases and Literature Review." Head and Neck Pathology (2016): n.
The present study included 331 patients with chronic gastritis with MDM2 SNP309 G/G genotype who had undergone esophagogastroduodenoscopy and screening colonoscopy.
The cohort was retrospectively collected from the institutional database and electronic medical records were reviewed for patient demographics, available MRI, and MDM2 pathologic diagnosis.
In clinical samples, increase in MDM2 gene amplification and cytoplasmic expression are observed in colon cancer, which is associated with advanced cancer staging [13].
As for MDM2, its level is regulated by SUMO-1; under normal conditions, MDM2 is undergoing self-ubiquitination and proteasomal degradation; in case of DNA damage, SUMO-1 binds MDM2 and abrogates its self-ubiquitination, leading to an increase in MDM2 ubiquitin ligase activity towards p53.
WDL and DDL show high-level amplification of CDK4 and MDM2, which are useful for differential diagnosis from other adipocytic tumors [9].
FISH and MDM2 studies could not be performed due to lack of specimen.
Therefore, the diagnosis of liposarcoma requires microscopic examination, and in many instances molecular testing including the determination of MDM2 status.
Among 200 studied SNPs in more than 30 candidate genes, the "Retina 4 Project" identified 8 SNPs in 7 genes, encoding CCL2, FGF2, IL1RN, LTA, NFKBIA, SMAD7, and TGFB2, as significant individual predictors for PVR [11] and demonstrated associations between PVR and SNPs in BAX, p53, PIK3CG, MDM2, SMAD7, and TNFB2 in the TNF locus [10,16-19].
Also, it was negative for S-100P, cytokeratin, epithelial membrane antigen, desmin, CD34, smooth muscle antigen, MDM2, and CDK4.