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Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53.

The human topoisomerase I- and p53-binding protein topors contains a highly conserved, N-terminal C3HC4-type RING domain that is homologous to the RING domains of known E3 ubiquitin ligases. We demonstrate that topors functions in vitro as a RING-dependent E3 ubiquitin ligase with the E2 enzymes UbcH5a, UbcH5c, and UbcH6 but not with UbcH7, CDC34, or UbcH2b. Additional studies indicate that a conserved tryptophan within the topors RING domain is required for ubiquitination activity. Furthermore, both in vitro and cellular studies implicate p53 as a ubiquitination substrate for topors. Similar to MDM2, overexpression of topors results in a proteasome-dependent decrease in p53 protein expression in a human osteosarcoma cell line. These results are similar to the recent finding that a Drosophila topors orthologue ubiquitinates the Hairy transcriptional repressor and suggest that topors functions as a ubiquitin ligase for multiple transcription factors.

Pubmed ID: 15247280


  • Rajendra R
  • Malegaonkar D
  • Pungaliya P
  • Marshall H
  • Rasheed Z
  • Brownell J
  • Liu LF
  • Lutzker S
  • Saleem A
  • Rubin EH


The Journal of biological chemistry

Publication Data

August 27, 2004

Associated Grants

  • Agency: NCI NIH HHS, Id: CA 39662
  • Agency: NIGMS NIH HHS, Id: GM 59170

Mesh Terms

  • Amino Acid Sequence
  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • Carrier Proteins
  • Cell Line, Tumor
  • Cysteine Endopeptidases
  • DNA-Binding Proteins
  • Drosophila
  • Electrophoresis, Polyacrylamide Gel
  • Glutathione Transferase
  • Green Fluorescent Proteins
  • Humans
  • Immediate-Early Proteins
  • Immunoblotting
  • Iron-Binding Proteins
  • Luminescent Proteins
  • Mass Spectrometry
  • Molecular Sequence Data
  • Multienzyme Complexes
  • Neoplasm Proteins
  • Nuclear Proteins
  • Plasmids
  • Proteasome Endopeptidase Complex
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-mdm2
  • Recombinant Proteins
  • Sequence Homology, Amino Acid
  • Silver Staining
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Transcription Factors
  • Transcription, Genetic
  • Transfection
  • Tryptophan
  • Tumor Suppressor Protein p53
  • Ubiquitin
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitin-Protein Ligase Complexes
  • Ubiquitin-Protein Ligases