Covalent modification of the androgen receptor by small ubiquitin-like modifier 1 (SUMO-1)

Modification by SUMO-1 is proposed to play a role in protein targeting and/ or stability. The SUMO-1-conjugating enzyme Ubc9 interacts with androgen re ceptor (AR), a ligand-activated transcription factor belonging to the stero id receptor superfamily. We show here that AR is covalently modified by SUM O-1 (sumoylated) in an androgen-enhanced fashion and identify the principal acceptor site in the N-terminal domain of AR. Substitutions of sumoylated Lys residues enhanced transcriptional activity of AR without influencing it s transrepressing activity. Interestingly, the same Lys residues form the c ores of the recently described transcriptional synergy control motifs in AR [Iniguez-Lluhi, J, A. & Pearce, D. (2000) Mol. Cell. Biol. 20, 6040-6050]. These motifs, which match perfectly with the sumoylation consensus sequenc e, are also present in the N-terminal domains of glucocorticoid, mineratoco rticoid, and progesterone receptor. Taken together, our data suggest that r eversible sumoylation is a mechanism for regulation of steroid receptor fun ction.