Regulation of Stat1 protein expression by phenylalanine 172 in the coiled-coil domain

Biochem Biophys Res Commun. 2006 Aug 4;346(3):1062-6. doi: 10.1016/j.bbrc.2006.06.026. Epub 2006 Jun 12.

Abstract

Stat1 plays an essential role in signal transduction and gene expression of various cytokines including interferons (IFNs). Although the mechanism of cytokine-induced activation of Stat1 and transcriptional regulation of Stat1 gene expression have been established, post-transcriptional regulation of Stat1 protein expression is not fully understood. Here, we report identification of a mutant of Stat1 that has decreased expression levels by using inducible translocation trap (ITT), a reporter gene-based detection system of nuclear translocation. The substitution of serine for phenylalanine 172 (F172S) in the coiled-coil domain causes marked decrease in Stat1 protein expression in various cell lines without decreasing its mRNA levels. Our results suggest that the decrease is caused by translational/post-translational mechanisms independent of proteasome machinery. These results suggest a novel potential mechanism of determination of specificity of Stat proteins and showed that the ITT system is a powerful technique to identify mutants of nuclear translocating signal transducers.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Chlorocebus aethiops
  • Conserved Sequence
  • Gene Expression Regulation*
  • Humans
  • Interferon-gamma / pharmacology
  • Mice
  • Molecular Sequence Data
  • Mutation / genetics
  • Phenylalanine / genetics
  • Phenylalanine / metabolism*
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors
  • Protein Biosynthesis / genetics
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • STAT1 Transcription Factor / chemistry*
  • STAT1 Transcription Factor / deficiency
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism*
  • Sequence Alignment

Substances

  • Proteasome Inhibitors
  • STAT1 Transcription Factor
  • Phenylalanine
  • Interferon-gamma
  • Proteasome Endopeptidase Complex