title: SUMO-1 modification represses Sp3 transcriptional activation and modulates its subnuclear localization.
abstract: The GC box binding transcription factor Sp3 both activates and represses transcription. We have found that Sp3 activity is regulated by SUMO-1 modification. Endogenous Sp3 is sumoylated and localized to the nuclear periphery and in nuclear dots. Removal of SUMO-1 from Sp3 by mutation of the SUMO acceptor lysines or expression of the SUMO-1 protease SuPr-1 converted Sp3 to a strong activator with a diffuse nuclear localization. Covalent attachment of SUMO-1 to Sp3 by gene fusion was sufficient to repress Sp3-dependent transcription and relocalize Sp3 to the nuclear periphery and nuclear dots. These studies reveal a direct effect of SUMO-1 modification on activity of a dual function transcription factor and provide a mechanism for functional specificity within the Sp transcription factor family.
authors.affiliation: Department of Pathology, Harvard Medical School, Children's Hospital, Boston, MA 02115, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ross
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Best
authors.forename: Leonard I
authors.initials: LI
authors.lastname: Zon
authors.forename: Grace
authors.initials: G
authors.lastname: Gill
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D022003:Cell Nucleus Structures / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D025842:SUMO-1 Protein / Q000378:metabolism*; D051705:Sp3 Transcription Factor; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D025842:SUMO-1 Protein; D014157:Transcription Factors; D051705:Sp3 Transcription Factor; D003546:Cysteine Endopeptidases; C501833:SENP2 protein, human; C408873:SENP6 protein, human