Encyclopedia of Cancer

Living Edition
| Editors: Manfred Schwab

MDM2

Living reference work entry
DOI: https://doi.org/10.1007/978-3-642-27841-9_3582-6

Definition

The protein human homologue of mouse double minute 2 (MDM2) was first identified as the product of the MDM2 gene amplified in transformed murine cells. It is a p53-binding nuclear protein that antagonizes and downregulates p53 activity. The gene maps to 12q14–q15 and is amplified in certain human tumors, including sarcomas, glioblastomas, and astrocytomas.

Characteristics

Discovery and Significance

MDM2 was discovered by Donna George’s laboratory as a gene that is amplified within double-minute chromosomes in 3T3DM cells and encodes a cellular transforming activity that promotes tumorigenicity in xenografts. Its association with p53 was first observed in immunoprecipitation analyses of p53 as a coprecipitating protein migrating with an apparent molecular weight of 95 kDa. Subsequently, it was shown that overexpression of MDM2 leads to increased degradation of p53 via the proteasome, thereby establishing its role as a crucial regulator of p53 levels.

Function

MDM2 is a...

Keywords

Zinc Finger Ring Finger Acidic Domain MDM4 Protein Ring Finger Domain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

References

  1. Bond GL, Levine AJ (2007) A single nucleotide polymorphism in the p53 pathway interacts with gender, environmental stresses and tumor genetics to influence cancer in humans. Oncogene 26:1317–1323CrossRefPubMedGoogle Scholar
  2. Bouska A, Eischen CM (2009) Murine double minute 2: p53-independent roads lead to genome instability or death. Trends Biochem Sci 34:279–286CrossRefPubMedGoogle Scholar
  3. Brown CJ, Cheok CF, Verma CS, Lane DP (2011) Reactivation of p53: from peptides to small molecules. Trends Pharmacol Sci 32:53–62CrossRefPubMedGoogle Scholar
  4. Lipkowitz S, Weissman AM (2011) RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nat Rev Cancer 11:629–643PubMedCentralCrossRefPubMedGoogle Scholar
  5. Miliani de Marval PL, Zhang Y (2011) The RP-Mdm2-p53 pathway and tumorigenesis. Oncotarget 2:234–238PubMedCentralPubMedGoogle Scholar
  6. Onel K, Cordon-Cardo C (2004) MDM2 and prognosis. Mol Cancer Res 2:1–8PubMedGoogle Scholar
  7. Wade M, Wang YV, Wahl GM (2010) The p53 orchestra: Mdm2 and Mdmx set the tone. Trends Cell Biol 20:299–309PubMedCentralCrossRefPubMedGoogle Scholar
  8. Wade M, Li YC, Wahl GM (2013) MDM2, MDMX and p53 in oncogenesis and cancer therapy. Nat Rev Cancer 13:83–96PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Division of Cancer Research, Jacqui Wood Cancer Centre/CRCUniversity of DundeeDundeeUK