title: SUMOylation of the corepressor N-CoR modulates its capacity to repress transcription.
abstract: 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.
authors.affiliation: Institute for Biomedical Research Georg-Speyer-Haus, 60596 Frankfurt, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Tiefenbach
authors.forename: Natalia
authors.initials: N
authors.lastname: Novac
authors.forename: Miryam
authors.initials: M
authors.lastname: Ducasse
authors.forename: Maresa
authors.initials: M
authors.lastname: Eck
authors.forename: Frauke
authors.initials: F
authors.lastname: Melchior
authors.forename: Thorsten
authors.initials: T
authors.lastname: Heinzel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051379:Mice; D009088:Mucoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056971:Nuclear Receptor Co-Repressor 1; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D046188:Protein Modification, Translational; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D009088:Mucoproteins; C539128:Ncor1 protein, mouse; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D050828:Protein Inhibitors of Activated STAT; D012097:Repressor Proteins; D025842:SUMO-1 Protein; C010393:lysin, gastropoda; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9