Ubc9 interacts with the androgen receptor and activates receptor-dependenttranscription

Ubc9, a homologue of the class E2 ubiquitin-conjugating enzymes, has recent ly been shown to catalyze conjugation of a small ubiquitin-like molecule-1 (SUMO-1) to a variety of target proteins. SUMO-1 modifications have been im plicated in the targeting of proteins to the nuclear envelope and certain i ntranuclear structures and in converting proteins resistant to ubiquitin-me diated degradation, In the present work, we find that Ubc9 interacts with t he androgen receptor (AR), a member of the steroid receptor family of ligan d-activated transcription factors. In transiently transfected COS-1 cells, AR dependent but not basal transcription is enhanced by the coexpression of Ubc9. The N-terminal half of the AR hinge region containing the C-terminal part of the bipartite nuclear localization signal is essential for the int eraction with Ubc9, Deletion of this part of the nuclear localization signa l, which does not completely prevent the transfer of AR to the nucleus, abo lishes the AR-Ubc9 interaction and attenuates the transcriptional response to cotransfected Ubc9, The C93S substitution of Ubc9, which prevents SUMO-1 conjugation by abrogating the formation of a thiolester bond between SUMO- 1 and Ubc9, does not influence the capability of Ubc9 to stimulate AR-depen dent transactivation, implying that Ubc9 is able to act as an AR coregulato r in a fashion independent of its ability to catalyze SUMO-1 conjugation.