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The MDM2 RING-finger domain is required to promote p53 nuclear export.

MDM2 can bind to p53 and promote its ubiquitination and subsequent degradation by the proteasome. Current models propose that nuclear export of p53 is required for MDM2-mediated degradation, although the function of MDM2 in p53 nuclear export has not been clarified. Here we show that MDM2 can promote the nuclear export of p53 in transiently transfected cells. This activity requires the nuclear-export signal (NES) of p53, but not the NES of MDM2. A mutation within the MDM2 RING-finger domain that inhibits p53 ubiquitination also inhibits the ability of MDM2 to promote p53 nuclear export. Finally, inhibition of nuclear export stabilizes wild-type p53 and leads to accumulation of ubiquitinated p53 in the nucleus. Our results indicate that MDM2-mediated ubiquitination, or other activities associated with the RING-finger domain, can stimulate the export of p53 to the cytoplasm through the activity of the p53 NES.

Pubmed ID: 10980696

Authors

  • Geyer RK
  • Yu ZK
  • Maki CG

Journal

Nature cell biology

Publication Data

September 22, 2000

Associated Grants

  • Agency: NCI NIH HHS, Id: 1R01CA80918

Mesh Terms

  • Active Transport, Cell Nucleus
  • Cell Nucleus
  • Humans
  • Nuclear Proteins
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-mdm2
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53
  • Ubiquitins
  • Zinc Fingers