Oncoprotein MDM2 Is a Ubiquitin Ligase E3 for Tumor Suppressor p53

FEBS Lett. 1997 Dec 22;420(1):25-7. doi: 10.1016/s0014-5793(97)01480-4.

Abstract

The tumor suppressor p53 is degraded by the ubiquitin-proteasome system. p53 was polyubiquitinated in the presence of E1, UbcH5 as E2 and MDM2 oncoprotein. A ubiquitin molecule bound MDM2 through sulfhydroxy bond which is characteristic of ubiquitin ligase (E3)-ubiquitin binding. The cysteine residue in the carboxyl terminus of MDM2 was essential for the activity. These data suggest that the MDM2 protein, which is induced by p53, functions as a ubiquitin ligase, E3, in human papillomavirus-uninfected cells which do not have E6 protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Extracts
  • HeLa Cells
  • Humans
  • Ligases / chemistry
  • Ligases / metabolism*
  • Molecular Sequence Data
  • Nuclear Proteins*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-mdm2
  • Sequence Analysis
  • Tumor Suppressor Protein p53 / metabolism*
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitins / metabolism*

Substances

  • Cell Extracts
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Tumor Suppressor Protein p53
  • Ubiquitins
  • Ubiquitin-Conjugating Enzymes
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Ligases