MDM2 and MDMX bind and stabilize the p53-related protein p73

Curr Biol. 1999 Jul 29-Aug 12;9(15):829-32. doi: 10.1016/s0960-9822(99)80367-4.

Abstract

The p53 gene encodes one of the most important tumor suppressors in human cells and undergoes frequent mutational inactivation in cancers. MDM2, a transcriptional target of p53, binds p53 and can both inhibit p53-mediated transcription [1] [2] and target p53 for proteasome-mediated proteolysis [3] [4]. A close relative of p53, p73, has recently been identified [5] [6]. Here, we report that, like p53, p73alpha and the alternative transcription product p73beta also bind MDM2. Interaction between MDM2 and p53 represents a key step in the regulation of p53, as MDM2 promotes the degradation of p53. In striking contrast to p53, the half-life of p73 was found to be increased by binding to MDM2. Like MDM2, the MDM2-related protein MDMX also bound p73 and stabilized the level of p73. Moreover, the growth suppression functions of p73 and the induction of endogenous p21, a major mediator of the p53-dependent growth arrest pathway, were enhanced in the presence of MDM2. These differences between the regulation of p53 and p73 by MDM2/MDMX may highlight a physiological difference in their action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division
  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drug Stability
  • Genes, Tumor Suppressor
  • Half-Life
  • HeLa Cells
  • Humans
  • In Vitro Techniques
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-mdm2
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Transfection
  • Tumor Protein p73
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • TP73 protein, human
  • Tumor Protein p73
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2