Regulation of nuclear receptor and coactivator functions by the carboxyl terminus of ubiquitin-conjugating enzyme 9

Int J Biochem Cell Biol. 2007;39(5):1035-46. doi: 10.1016/j.biocel.2007.02.002. Epub 2007 Feb 6.


Small ubiquitin-related modifier (SUMO) is a protein moiety that is ligated to lysine residues in a variety of target proteins. The SUMO E2 enzyme ubiquitin-conjugating enzyme 9 (Ubc9) is sufficient for substrate recognition and lysine modification of known SUMO targets. Previous studies have demonstrated that mutated Ubc9 that has lost its SUMO-ligating activity retains its enhancement on transactivation mediated by androgen receptor (AR). In contrast to the binding ability to Ubc9, the sumoylation of AR via the association of SUMO-1 and PIAS1 is able to repress AR-dependent transcription. In the present study, we present several lines of evidence to explain the role of over-expressed Ubc9 as a cofactor in the nuclear receptor and coactivator functions, including (i) activity that is independent of its ability to catalyze SUMO-1 conjugation, (ii) an insight into the protein-protein interaction motif in its eight C-terminal residues, (iii) selective coactivator function in nuclear receptor-relevant transactivation activities, and (iv) a non-trichostatin A-sensitive autonomous transcription repression domain in its far C-terminal region. Taken together, our data suggest that the both the protein-protein interaction through the Ubc9 C-terminus and its sumoylation-modifying activity provide the mechanism for regulating nuclear receptor functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • COS Cells
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • HeLa Cells
  • Humans
  • Plasmids / genetics
  • Protein Binding
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Small Ubiquitin-Related Modifier Proteins / genetics
  • Small Ubiquitin-Related Modifier Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Transfection
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Conjugating Enzymes / metabolism*


  • Carrier Proteins
  • Receptors, Androgen
  • Receptors, Cytoplasmic and Nuclear
  • Small Ubiquitin-Related Modifier Proteins
  • Transcription Factors
  • Ubiquitin-Conjugating Enzymes