SUMO-1 modification represses Sp3 transcriptional activation and modulates its subnuclear localization.
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.
Ross
Sarah
S
Department of Pathology, Harvard Medical School, Children's Hospital, Boston, MA 02115, USA.
Best
Jennifer L
JL
Zon
Leonard I
LI
Gill
Grace
G
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
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