Small ubiquitin-related modifier-1 (SUMO-1) modification of the glucocorticoid receptor.
Small ubiquitin-related modifier-1 (SUMO-1) is covalently attached to many cellular targets to regulate protein-protein and protein-DNA interactions, as well as localization and stability of the target protein. The SUMO-1-conjugating E2 enzyme Ubc9 is known to interact with the glucocorticoid receptor (GR), a ligand-dependent transcription factor. In the present study, we show that GR is post-translationally modified by SUMO-1 (sumoylated) in a ligand-enhanced fashion. We identify experimentally three consensus SUMO attachment sites, two in the N-terminal transactivation region and one in the ligand-binding domain of GR. The two N-terminal sites are the major acceptor sites for SUMO-1 attachment. Mutation of these sites enhances transcriptional activity of GR on minimal promoters, but has no clear effect on the more complex mouse mammary tumour virus promoter. Thus SUMO-1 modification of GR influences receptor function in a promoter context-dependent fashion.
Tian
Sha
S
Biomedicum Helsinki, Institute of Biomedicine, University of Helsinki, P.O. Box 63 (Haartmaninkatu 8), FIN-00014 Helsinki, Finland.
Poukka
Hetti
H
Palvimo
Jorma J
JJ
Jänne
Olli A
OA
D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D006367:HeLa Cells; D006801:Humans; D008239:Lysine / Q000378:metabolism; D011233:Precipitin Tests; D011499:Protein Processing, Post-Translational; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D025842:SUMO-1 Protein / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology
D011965:Receptors, Glucocorticoid; D025842:SUMO-1 Protein; D008239:Lysine