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. 2012 Mar;3(3-4):209-18.
doi: 10.1177/1947601912455324.

Using Mouse Models to Explore MDM-p53 Signaling in Development, Cell Growth, and Tumorigenesis

Hugh S Gannon  1 , Stephen N Jones
Affiliations

Using Mouse Models to Explore MDM-p53 Signaling in Development, Cell Growth, and Tumorigenesis

Hugh S Gannon et al. Genes Cancer. 2012 Mar.

Abstract

The p53 transcription factor regulates the expression of numerous genes whose products affect cell proliferation, senescence, cellular metabolism, apoptosis, and DNA repair. These p53-mediated effects can inhibit the growth of stressed or mutated cells and suppress tumorigenesis in the organism. However, the various growth-inhibitory properties of p53 must be kept in check in nondamaged cells in order to facilitate proper embryogenesis or the homeostatic maintenance of adult tissues. This requisite inhibition of p53 is performed primarily by the MDM oncoproteins, Mdm2 and MdmX. These p53-binding proteins limit p53 activity both in normal cells and in stressed cells seeking to promote resolution of their p53-stress response. Many mouse models bearing genetic alterations in Mdm2 or MdmX have been generated to explore the function and regulation of MDM-p53 signaling in development, in tissue homeostasis, in aging, and in cancer. These models not only have demonstrated a critical need for Mdm2 and MdmX in normal cell growth and in development but more recently have identified the MDM-p53 signaling axis as a key regulator of the cellular response to a wide variety of genetic or metabolic stresses. In this review, we discuss what has been learned from various studies of these Mdm2 and MdmX mouse models and highlight a few of the many important remaining questions.

Keywords: Mdm2; MdmX; mouse models; p53.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
The Mdm2-MdmX-p53 signaling pathway. Mdm2 and MdmX expression is upregulated by p53 due to the presence of intragenic p53 promoter response elements (triangles). The subsequent increase in MDM proteins results in the inhibition of p53 functions due to p53 and Mdm2/MdmX complex formation.
Figure 2.
Figure 2.
Proposed functional domains of the Mdm2 and MdmX oncoproteins. The percentages of identities of the individual domains shared by the 2 MDM proteins are shown. NLS = nuclear localization signal; NES = nuclear export signal; Zn finger = Zinc finger.
See this image and copyright information in PMC

References

    1. Vousden KH, Lu X. Live or let die: the cell’s response to p53. Nat Rev Cancer. 2002;2: 594-604 - PubMed
    1. Vousden KH, Ryan KM. p53 and metabolism. Nat Rev Cancer. 2009;9:691-700 - PubMed
    1. Sengupta S, Harris CC. p53: traffic cop at the crossroads of DNA repair and recombination. Nat Rev Mol Cell Biol. 2005;6:44-55 - PubMed
    1. Lane DP. Cancer. p53, guardian of the genome. Nature. 1992;358:15-6 - PubMed
    1. Soussi T, Beroud C. Assessing TP53 status in human tumours to evaluate clinical outcome. Nat Rev Cancer. 2001;1:233-40 - PubMed

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