New Glucocorticoid Receptor Partner?

Abstract

Ubc9 is a human protein homolog of a yeast protein that is an E2 ubiquitin-conjugating enzyme. Ubc9 can promote conjugation of SUMO-1 (small ubiquitin-like modifier-1) to its various binding partners and thereby modifiy their function. Kaul et al. present evidence for a new role of Ubc9--regulation of transcriptional activation by the glucocorticoid receptor (GR). The authors found Ubc9 in a yeast two-hybrid screen for proteins that interact with the glucocorticoid modulatory element binding factors 1 and 2 (GMEB-1 and GMEB-2). GMEBs bind to DNA, glucocorticoid receptors, and coactivators and can inhibit transcriptional activity of the GR and decrease sensitivity of the receptor to agonists. Ubc9 also interacted in mammalian two-hybrid or pull-down assays with the GR itself. In transfected cells, Ubc9 increased transcriptional activity of GR and, when GR was expressed in large amounts, Ubc9 enhanced sensitivity of the GR to agonists and also modulated the response to GR antagonists. Unexpectedly, these effects did not require the sumoylation activity of Ubc9 and were even observed in the absence of glucocorticoid modulatory element. Assuming similar effects are mediated by endogenous Ubc9, the results indicate that Ubc9 may be a transcriptional adapter that helps control transcriptional activation by steroid receptors. S. Kaul, J. A. Blackford Jr., S. Cho, S. S. Simons Jr., Ubc9 is a novel modulator of the induction properties of glucocorticoid receptors. J. Biol. Chem. 277 , 12541-12549 (2002). [Abstract] [Full Text]