SUMO-1 modification represses Sp3 transcriptional activation and modulates its subnuclear localization

Mol Cell. 2002 Oct;10(4):831-42. doi: 10.1016/s1097-2765(02)00682-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Cell Line
  • Cell Nucleus Structures / metabolism*
  • Cysteine Endopeptidases / metabolism
  • DNA-Binding Proteins / antagonists & inhibitors*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Transport
  • SUMO-1 Protein / metabolism*
  • Sp3 Transcription Factor
  • Transcription Factors / antagonists & inhibitors*
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Transcriptional Activation*

Substances

  • DNA-Binding Proteins
  • SUMO-1 Protein
  • Transcription Factors
  • Sp3 Transcription Factor
  • Cysteine Endopeptidases
  • SENP2 protein, human
  • SENP6 protein, human