GSBS Student Publications

Title

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

Student Author(s)

Hugh Gannon

GSBS Program

Cell Biology

UMMS Affiliation

Department of Cell and Developmental Biology

Date

11-15-2012

Document Type

Article

Disciplines

Cancer Biology | Cell and Developmental Biology | Computational Biology

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.

Rights and Permissions

Citation: Genes Cancer. 2012 Mar;3(3-4):209-18. doi: 10.1177/1947601912455324. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal Title

Genes and cancer

PubMed ID

23150754