Regulation of nuclear receptor and coactivator functions by the carboxyl terminus of ubiquitin-conjugating enzyme 9.
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.
Chang
Yung-Lung
YL
Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, ROC.
Huang
Chi-Jung
CJ
Chan
James Yi-Hsin
JY
Liu
Pei-Yao
PY
Chang
Hui-Ping
HP
Huang
Shih-Ming
SM
D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D044763:Ubiquitin-Conjugating Enzymes