Keeping p53 in check: essential and synergistic functions of Mdm2 and Mdm4.
Citations
186 citations
Cites background from "Keeping p53 in check: essential and..."
...This is why they are frequently overproduced through gene amplification and/or overexpression in tumors that retain wildtype p53 (14)....
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...The functional relationship between MDM2 and MDMX is still being refined at the molecular level, but it is well established that these two negative regulators play a critical role in controlling p53 tumor-suppressor function in normal cells (2, 14)....
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...Similar to MDM2, MDMX overexpression has been shown to effectively disable this function by inhibiting p53 transcriptional activity (6, 14)....
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176 citations
174 citations
Cites background from "Keeping p53 in check: essential and..."
...MDM-2 functions in a heterodimeric complex with MDM-4, a related protein that can bind to p53 and MDM-4 and regulates MDM-2 activity (5)....
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173 citations
Cites background from "Keeping p53 in check: essential and..."
...MDM2 is responsible for the maintenance of the basal, inactive state of p53 under normal conditions (Marine et al., 2006)....
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173 citations
Cites background from "Keeping p53 in check: essential and..."
...Studies in mice have indicated that an effect of MDMX on p53 stability, through the modulation of MDM2, can be seen in some but not all tissues (Marine et al, 2006)....
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...The MDM2-related protein MDMX also plays an important role in the regulation of p53, both by binding directly to p53 and through interaction with MDM2 (Marine et al, 2006)....
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...The current data most strongly support a model in which MDM2 regulates p53 by targeting it for degradation, whereas MDMX functions by directly inhibiting the transcriptional activity of p53 by binding to its N-terminal transactivation domain (Marine et al, 2006)....
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