Regulation of gene-activation pathways by PIAS proteins in the immune system

Nat Rev Immunol. 2005 Aug;5(8):593-605. doi: 10.1038/nri1667.


The protein inhibitor of activated STAT (PIAS) family of proteins has been proposed to regulate the activity of many transcription factors, including signal transducer and activator of transcription proteins (STATs), nuclear factor-kappaB, SMA- and MAD-related proteins (SMADs), and the tumour-suppressor protein p53. PIAS proteins regulate transcription through several mechanisms, including blocking the DNA-binding activity of transcription factors, recruiting transcriptional corepressors or co-activators, and promoting protein sumoylation. Recent genetic studies support an in vivo function for PIAS proteins in the regulation of innate immune responses. In this article, we review the current understanding of the molecular basis, specificity and physiological roles of PIAS proteins in the regulation of gene-activation pathways in the immune system.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Cycle / genetics
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Gene Expression Regulation*
  • Humans
  • Immune System / metabolism*
  • Protein Inhibitors of Activated STAT
  • Protein Structure, Secondary
  • Proteins / chemistry
  • Proteins / metabolism*
  • Signal Transduction / genetics
  • Transcriptional Activation


  • Cytokines
  • Protein Inhibitors of Activated STAT
  • Proteins