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

被引:356
作者
Poukka, H
Karvonen, U
Jänne, OA
Palvimo, JJ [1 ]
机构
[1] Univ Helsinki, Inst Biomed, Dept Physiol, FIN-00014 Helsinki, Finland
[2] Univ Helsinki, Dept Clin Chem, FIN-00014 Helsinki, Finland
关键词
D O I
10.1073/pnas.97.26.14145
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 receptor (AR), a ligand-activated transcription factor belonging to the steroid receptor superfamily. We show here that AR is covalently modified by SUMO-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 its transrepressing activity. Interestingly, the same Lys residues form the cores 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 sequence, are also present in the N-terminal domains of glucocorticoid, mineratocorticoid, and progesterone receptor. Taken together, our data suggest that reversible sumoylation is a mechanism for regulation of steroid receptor function.
引用
收藏
页码:14145 / 14150
页数:6
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