Mdmx and Mdm2: brothers in arms?
The p53 tumor suppressor pathway is inactivated in most if not all human tumors. In about 50% of the cases this is accomplished directly by gene mutations. The tumors that retain wild type p53 frequently show defects either in effector target genes, or in the expression of p53 regulatory proteins. The Mdm2 protein is generally considered THE master regulator of the p53 tumor suppressor activity. Recently, however, the Mdm2-related protein Mdmx is taking the stage in the p53-Mdm2-Mdmx play. We summarize here observations unambiguously assigning a critical role for the Mdmx protein in the regulation of p53 function during development and tumor formation.
Marine
Jean-Christophe
JC
Laboratory For Molecular Cancer Biology, Flanders Interuniversity Institute for Biotechnology (VIB), Ghent, Belgium.
Jochemsen
Aart G
AG
D000818:Animals; D018797:Cell Cycle Proteins; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D025461:Feedback, Physiological / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009857:Oncogenes / Q000235:genetics; D010802:Phylogeny; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2