title: Co-repressor activity of scaffold attachment factor B1 requires sumoylation.
abstract: Sumoylation is an emerging modification associated with a variety of cellular processes including the regulation of transcriptional activities of nuclear receptors and their coregulators. As SUMO modifications are often associated with transcriptional repression, we examined if sumoylation was involved in modulation of the transcriptional repressive activity of scaffold attachment factor B1. Here we show that SAFB1 is modified by both the SUMO1 and SUMO2/3 family of proteins, on lysine's K231 and K294. Further, we demonstrate that SAFB1 can interact with PIAS1, a SUMO E3 ligase which mediates SAFB1 sumoylation. Additionally, SENP1 was identified as the enzyme desumoylating SAFB1. Mutation of the SAFB1 sumoylation sites lead to a loss of transcriptional repression, at least in part due to decreased interaction with HDAC3, a known transcriptional repressor and SAFB1 binding partner. In summary, the transcriptional repressor SAFB1 is modified by both SUMO1 and SUMO2/3, and this modification is necessary for its full repressive activity.
authors.affiliation: Breast Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Garee
authors.forename: Rene
authors.initials: R
authors.lastname: Meyer
authors.forename: Steffi
authors.initials: S
authors.lastname: Oesterreich
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D056970:Co-Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016384:Consensus Sequence; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D025842:SUMO-1 Protein; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D058207:Sumoylation; D014158:Transcription, Genetic; D014452:Ubiquitins
chemical_list: D056970:Co-Repressor Proteins; D036961:Matrix Attachment Region Binding Proteins; D034521:Nuclear Matrix-Associated Proteins; C106529:PIAS1 protein, human; D050828:Protein Inhibitors of Activated STAT; D011960:Receptors, Estrogen; C109132:SAFB protein, human; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; C117909:SUMO2 protein, human; C492189:SUMO3 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014452:Ubiquitins