The mdm network and its regulation of p53 activities: A rheostat of cancer risk

Christine M. Eischen, Guillermina Lozano

Research output: Contribution to journalReview articlepeer-review

65 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)728-737
Number of pages10
JournalHuman mutation
Volume35
Issue number6
DOIs
StatePublished - Jun 2014

Keywords

  • Mdm2
  • Mdm4
  • Mouse models
  • P53
  • TCGA
  • TP53
  • Trp53

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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