2017
DOI: 10.1158/0008-5472.can-17-0809
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Mdm2 Is Required for Survival and Growth of p53-Deficient Cancer Cells

Abstract: p53 deletion prevents the embryonic lethality of normal tissues lacking Mdm2, suggesting that cells can survive without Mdm2 if p53 is also absent. Here we report evidence challenging this view, with implications for therapeutically targeting Mdm2. Deletion of Mdm2 in T cell lymphomas or sarcomas lacking p53 induced apoptosis and G2 cell cycle arrest, prolonging survival of mice with these tumors. p53−/− fibroblasts showed similar results, indicating that the effects of Mdm2 loss extend to pre-malignant cells.… Show more

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Cited by 47 publications
(40 citation statements)
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“…MDM2 is reported to directly interact with histones and ubiquitinate histone H2A [37]. What is more, MDM2 plays repressing roles in several genes' expression, such as p53, which explains its tumourpromoting effects [38]. According to these evidences, Ras-ERK1/2 signalling repressed H2A.X phosphorylation to play tumour-promoting function possibly through MDM2-mediated degradation of JMJD6.…”
Section: Discussionmentioning
confidence: 99%
“…MDM2 is reported to directly interact with histones and ubiquitinate histone H2A [37]. What is more, MDM2 plays repressing roles in several genes' expression, such as p53, which explains its tumourpromoting effects [38]. According to these evidences, Ras-ERK1/2 signalling repressed H2A.X phosphorylation to play tumour-promoting function possibly through MDM2-mediated degradation of JMJD6.…”
Section: Discussionmentioning
confidence: 99%
“…In p53-deficient lymphomas and sarcomas, the deletion of MDM2 could still induce apoptosis and cell cycle arrest through activation of p53 target genes, which were mediated by the stabilization of p73 [249]. Along the same lines, another study found that p73 deletion augmented the effects of MDM2 overexpression in the development of B-cell lymphomagenesis in mice, which was shown to promote genomic instability and tumor development [250].…”
Section: Mdm2/mdmxmentioning
confidence: 93%
“…Reports have indicated that p73 plays a key role in cancer growth and progression via MDM2 regulation in p53 mutated breast cancers [27,42,43] . We observed that BAI1 had no signi cant in uence on the mRNA and protein expression of p73.…”
Section: Discussionmentioning
confidence: 99%
“…However, the interaction between MDM2 and p73 negatively regulates the transcriptional activity of p73 but slightly impacts its degradation which distinct from the mechanism used for p53 regulation [25,26] . Previous studies found that MDM2 deletion increased levels of p73, then induced apoptosis and G2 cell-cycle arrest, which compensates for the loss of p53 in p53-de cient cancers [27] . Therefore, p73 provides a legitimate and attractive target in cells lacking functional p53 and provides a promising strategy for cancer therapy.…”
Section: Introductionmentioning
confidence: 87%