Keeping p53 in check: essential and synergistic functions of Mdm2 and Mdm4.
Citations
12 citations
Cites background from "Keeping p53 in check: essential and..."
...One important antagonist, MDM2, is essential for ubiquitylation and subsequent degradation of p53 to maintain it at low levels in unstressed cells [6]....
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12 citations
Cites background from "Keeping p53 in check: essential and..."
...Under normal growth conditions, p53 activity is tightly controlled by MDM family members, MDM2 and MDM4, and their derivative forms (Marine et al., 2006; Toledo and Wahl 2007; Mancini et al., 2009a)....
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...In normal growing cells, p53 is regulated in a non-redundant manner by MDM family members, MDM4 and MDM2 (Marine et al., 2006)....
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...Overall, the consequences of p76MDM2-mediated regulation of MDM4 are the attenuation of MDM4 and MDM2 inhibitory activity toward p53, pointing to p76MDM2 as an important factor in the positive control of p53 function....
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...MDM4 is an inhibitor of p53 activity under normal growth conditions (Marine et al., 2006; Wang et al., 2009), whereas it exerts a positive function toward p53-mediated apoptosis upon lethal DNA damage (Mancini and Moretti, 2009)....
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12 citations
Cites background from "Keeping p53 in check: essential and..."
...Conversely, the interaction of MDMX with the trans-activation function of p53 does not target the tumor suppressor protein for the degradation, but inactivates its transcriptional activity [3,4]....
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12 citations
Cites background from "Keeping p53 in check: essential and..."
...This physical interaction prevents p53 from interacting with its transcription factors.([22]) Mdm2 also induces p53 degradation by the ubiquitylation function of the E3 ubiquitin ligase....
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...In cells undergoing stress, the physical interaction between p53 and Mdm2 (an E3 ubiquitin ligase that binds and targets p53 for proteasomal degradation) is perturbed,([22]) leaving p53 unchecked to perform its biological functions....
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12 citations
Cites background from "Keeping p53 in check: essential and..."
...Several epidemiological studies have evaluated the connection of p53 R72P, MDM2 SNP309 and risk of different types of cancer (Marine et al., 2006; Sadeghi et al., 2013; Song et al., 2013)....
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...Clinical studies and mouse models have shown that p53 is mutated in 50% of human cancers, and functionally inactivated in much more (Marine et al., 2006)....
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...MDM2 is a crucial negative regulator of p53, that promote its degradation, as disclosed by models in which deletion of MDM2 gene is lethal in a p53-dependent manner (Marine et al., 2006; Ren et al., 2013)....
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