MDMX: from bench to bedside.
The tumor suppressor protein p53 is negatively regulated by Mdm2, a ubiquitin ligase protein that targets p53 for degradation. Mdmx (also known as Mdm4) is a relative of Mdm2 that was identified on the basis of its ability to physically interact with p53. An increasing body of evidence, including recent genetic studies, suggests that Mdmx also acts as a key negative regulator of p53. Aberrant expression of MDMX could thus contribute to tumor formation. Indeed, MDMX amplification and/or overexpression occurs in several diverse tumors. Strikingly, recent work identifies MDMX as a specific chemotherapeutic target for treatment of retinoblastoma. Specific MDMX antagonists should therefore be developed as a tool to ensure activation of 'dormant' p53 activity in tumors that retain wild-type p53.
Marine
Jean-Christophe W
JC
Laboratory For Molecular Cancer Biology, Flanders Interuniversity Institute for Biotechnology (VIB), University of Ghent, B-9052 Ghent, Belgium. chris.marine@dmbr.ugent.be
Dyer
Michael A
MA
Jochemsen
Aart G
AG
D000818:Animals; D018797:Cell Cycle Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000209:etiology; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53