Small ubiquitin-related modifier-1 (SUMO-1) modification of the glucocorticoid receptor

Biochem J. 2002 Nov 1;367(Pt 3):907-11. doi: 10.1042/BJ20021085.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • COS Cells
  • HeLa Cells
  • Humans
  • Lysine / metabolism
  • Precipitin Tests
  • Protein Processing, Post-Translational
  • Receptors, Glucocorticoid / chemistry
  • Receptors, Glucocorticoid / metabolism*
  • Receptors, Glucocorticoid / physiology
  • SUMO-1 Protein / metabolism*
  • Transcription, Genetic / physiology

Substances

  • Receptors, Glucocorticoid
  • SUMO-1 Protein
  • Lysine