Ubiquitination of E3 ubiquitin ligase TRIM5 alpha and its potential role

FEBS J. 2008 Apr;275(7):1540-55. doi: 10.1111/j.1742-4658.2008.06313.x. Epub 2008 Feb 25.


HIV-1 efficiently infects susceptible cells and causes AIDS in humans. Although HIV can also enter the cells of Old World monkeys, it encounters a block before reverse transcription. Data have shown that this species-specific restriction is mediated by tripartite motif (TRIM)5alpha, whose molecular function is still undefined. Here, we show that TRIM5alpha functions as a RING-finger-type E3 ubiquitin ligase both in vitro and in vivo and ubiquitinates itself in cooperation with the E2 ubiquitin-conjugating enzyme UbcH5B. In addition to the self-ubiquitination, we show that TRIM5alpha is ubiquitinated by another E3 ubiquitin ligase, Ro52, and deubiquitinated by YopJ, one of the pathogenic proteins derived from Yersinia species. Thus, the ubiquitination of TRIM5alpha is catalyzed by itself and Ro52 and downregulated by YopJ. Unexpectedly, although TRIM5alpha is ubiquitinated, our results have revealed that the proteasome inhibitors MG115 and MG132 do not stabilize it in HeLa cells, suggesting that the ubiquitination of TRIM5alpha does not lead to proteasomal degradation. Importantly, TRIM5alpha is clearly conjugated by a single ubiquitin molecule (monoubiquitination). Our monoubiquitin-fusion assay suggests that monoubiquitination is a signal for TRIM5alpha to translocate from cytoplasmic bodies to the cytoplasm.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Carrier Proteins / physiology
  • Cell Line
  • Cytoplasm / enzymology
  • Evolution, Molecular
  • HeLa Cells
  • Humans
  • Phylogeny
  • Ribonucleoproteins / chemistry
  • Ubiquitin / metabolism*
  • Ubiquitin-Conjugating Enzymes / chemistry
  • Ubiquitin-Conjugating Enzymes / metabolism
  • Ubiquitin-Conjugating Enzymes / physiology
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / metabolism*


  • Carrier Proteins
  • Ribonucleoproteins
  • SS-A antigen
  • Ubiquitin
  • UBE2D2 protein, human
  • Ubiquitin-Conjugating Enzymes
  • TRIM5 protein, human
  • Ubiquitin-Protein Ligases