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Vol. 17, Issue 4, 1643-1651, April 2006

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SUMOylation of the Corepressor N-CoR Modulates Its Capacity to Repress Transcription

Jens Tiefenbach ^* , Natalia Novac ^*, Miryam Ducasse ^*, Maresa Eck ^*, Frauke Melchior , and Thorsten Heinzel ^* 

^* Institute for Biomedical Research Georg-Speyer-Haus, 60596 Frankfurt, Germany; Department of Biochemistry I, University Göttingen, 37073 Göttingen, Germany

Submitted July 8, 2005; Revised December 2, 2005; Accepted January 10, 2006
Monitoring Editor: Thomas Sommer

In the absence of ligands the corepressor N-CoR mediates transcriptional repression by some nuclear hormone receptors. Several protein–protein interactions of N-CoR are known, of which mainly complex formation with histone deacetylases (HDACs) leads to the repression of target genes. On the other hand, the role of posttranslational modifications in corepressor function is not well established. Here, we show that N-CoR is modified by Sumo-1. We found SUMO-E2–conjugating enzyme Ubc9 and SUMO-E3 ligase Pias1 as novel N-CoR interaction partners. The SANT1 domain of N-CoR was found to mediate this interaction. We show that K152, K1117, and K1330 of N-CoR can be conjugated to SUMO and that mutation of all sites is necessary to fully block SUMOylation in vitro. Because these lysine residues are located within repression domains I and III, respectively, we investigated a possible correlation between the functions of the repression domains and SUMOylation. Coexpression of Ubc9 protein resulted in enhanced N-CoR–dependent transcriptional repression. Studies using SUMOylation-deficient N-CoR RDI mutants suggest that SUMO modification contributes to repression by N-CoR. Mutation of K152 to R in RD1, for example, not only significantly reduced repression of a reporter gene, but also abolished the effect of Ubc9 on transcriptional repression.

Present address: Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto and CCBR Building, 160 College Street, Toronto, Ontario M5S 3E1, Canada

Present address: Institute of Biochemistry and Biophysics, Friedrich-Schiller-University Jena, Philosophenweg 12, 07743 Jena, Germany.

Address correspondence to: Thorsten Heinzel (t.heinzel{at}uni-jena.de).

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