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

• Published in: The international journal of biochemistry & cell biology Vol. 39; no. 5; pp. 1035 - 1046
• Main Authors: Chang, Yung-Lung, Huang, Chi-Jung, Chan, James Yi-Hsin, Liu, Pei-Yao, Chang, Hui-Ping, Huang, Shih-Ming
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 2007
• Subjects: Animals; Blotting, Western; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Line, Tumor; Cercopithecus aethiops; Coactivation; COS Cells; HeLa Cells; Humans; Nuclear receptor; 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; Transactivation; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptional Activation; Transfection; Ubc9; Ubiquitin-Conjugating Enzymes - genetics; Ubiquitin-Conjugating Enzymes - metabolism; Coactivation; Nuclear receptor; Ubc9; Transactivation
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2007.02.002

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.