Format

Send to

Choose Destination
Hum Mutat. 2014 Jun;35(6):728-37. doi: 10.1002/humu.22524. Epub 2014 Mar 6.

The Mdm network and its regulation of p53 activities: a rheostat of cancer risk.

Author information

1
Vanderbilt University Medical Center, Department of Pathology, Microbiology and Immunology, Nashville, Tennessee.

Abstract

The potent transcriptional activity of p53 (Trp53, TP53) must be kept in check for normal cell growth and survival. Tumors, which drastically deviate from these parameters, have evolved multiple mechanisms to inactivate TP53, the most prevalent of which is the emergence of TP53 missense mutations, some of which have gain-of-function activities. Another important mechanism by which tumors bypass TP53 functions is via increased levels of two TP53 inhibitors, MDM2, and MDM4. Studies in humans and in mice reveal the complexity of TP53 regulation and the exquisite sensitivity of this pathway to small changes in regulation. Here, we summarize the factors that impinge on TP53 activity and thus cell death/arrest or tumor development.

KEYWORDS:

Mdm2; Mdm4; TCGA; TP53; Trp53; mouse models; p53

PMID:
24488925
PMCID:
PMC4725600
DOI:
10.1002/humu.22524
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center