Ubiquitin-dependent c-Jun degradation in vivo is mediated by the delta domain

Cell. 1994 Sep 9;78(5):787-98. doi: 10.1016/s0092-8674(94)90502-9.

Abstract

The role of the ubiquitin-dependent proteolysis system in c-Jun breakdown was investigated. Using in vitro experiments and a novel in vivo assay that utilizes molecularly-tagged ubiquitin and c-Jun proteins, it was shown that c-Jun, but not its transforming counterpart, retroviral v-Jun, can be efficiently multiubiquitinated. Consistently, v-Jun has a longer half-life than c-Jun. Mutagenesis experiments indicate that the reason for the escape of v-Jun from multiubiquitination and its resulting stabilization is the deletion of the delta domain, a stretch of 27 amino acids that is present in c-Jun but not in v-Jun. c-Jun sequences containing the delta domain, when transferred to the bacterial beta-galactosidase protein, function as a cis-acting ubiquitination and degradation signal. The correlation between transforming ability and the escape from ubiquitin-dependent degradation described here suggests a novel route to oncogenesis.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • Chickens
  • DNA Mutational Analysis
  • Endopeptidases / metabolism
  • HeLa Cells
  • Humans
  • Ligases / metabolism*
  • Lysine / metabolism
  • Molecular Sequence Data
  • Oncogene Protein p65(gag-jun) / metabolism
  • Protein Conformation
  • Protein Processing, Post-Translational
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Recombinant Proteins / metabolism
  • Regulatory Sequences, Nucleic Acid
  • Structure-Activity Relationship
  • Ubiquitins / genetics
  • Ubiquitins / metabolism*

Substances

  • Oncogene Protein p65(gag-jun)
  • Proto-Oncogene Proteins c-jun
  • Recombinant Proteins
  • Ubiquitins
  • Endopeptidases
  • Ligases
  • Lysine