PIAS proteins promote SUMO-1 conjugation to STAT1

Blood. 2003 Nov 1;102(9):3311-3. doi: 10.1182/blood-2002-12-3816. Epub 2003 Jul 10.


Signal transducer and activator of transcription 1 (STAT1) is a critical mediator of interferon-gamma (IFN-gamma)-induced transcription that is regulated through posttranslational modifications and through transacting proteins such as protein inhibitor of activated STAT1 (PIAS1). PIAS proteins have been shown to function as E3-type small ubiquitin-like modifier (SUMO) ligases, and sumoylation has been identified as a modulatory mechanism for several transcription factors. Here we show that STAT1 is subject to SUMO-1 modification, and sumoylation occurs in vivo and in vitro at a single, evolutionary conserved amino acid residue Lys703. Members of the PIAS family of proteins were found to strongly stimulate sumoylation of STAT1. Furthermore, activation of STAT1 by IFN-gamma or pervanadate induced SUMO-1 conjugation. Mutation of Lys703 in STAT1 resulted in increased IFN-gamma-mediated transactivation, suggesting a negative regulatory function for sumoylation. These results indicate that STAT1 is covalently modified by SUMO-1 in cytokine signaling and that PIAS proteins promote SUMO-1 conjugation to STAT1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Interferon-gamma / pharmacology
  • Mutation
  • Protein Inhibitors of Activated STAT
  • Protein Processing, Post-Translational
  • Proteins / physiology*
  • STAT1 Transcription Factor
  • SUMO-1 Protein / metabolism*
  • Signal Transduction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcriptional Activation
  • Vanadates / pharmacology


  • DNA-Binding Proteins
  • Protein Inhibitors of Activated STAT
  • Proteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • SUMO-1 Protein
  • Trans-Activators
  • pervanadate
  • Vanadates
  • Interferon-gamma