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A transcriptional corepressor of Stat1 with an essential LXXLL signature motif

B Liu1, M Gross, J ten Hoeve

  • 1Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles, CA 90095, USA.

Proceedings of the National Academy of Sciences of the United States of America
|March 15, 2001
PubMed

Insights

Protein inhibitor of activated STAT y (PIASy) acts as a transcriptional corepressor for Stat1. Interferon treatment causes Stat1 and PIASy to interact, repressing Stat1-mediated gene activation.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Signal Transduction

Background:

  • Interferon (IFN) treatment is known to induce tyrosine phosphorylation and nuclear translocation of signal transducer and activator of transcription 1 (Stat1).
  • Stat1 plays a crucial role in activating or repressing gene transcription following IFN stimulation.
  • Understanding the regulatory mechanisms of Stat1 activity is essential for comprehending cellular responses to interferons.

Purpose of the Study:

  • To identify novel regulators of Stat1 transcriptional activity.
  • To investigate the role of the protein inhibitor of activated STAT (PIAS) family in Stat1-mediated gene regulation.
  • To elucidate the mechanism by which PIASy interacts with and modulates Stat1 function.

Main Methods:

  • In vivo interaction studies to assess Stat1-PIASy complex formation upon IFN treatment.
  • Analysis of Stat1 DNA binding activity in the presence of PIASy.
  • Site-directed mutagenesis to investigate the role of the LXXLL motif in PIASy's transrepression activity.

Main Results:

  • PIASy was identified as a transcriptional corepressor of Stat1.
  • IFN treatment induced the in vivo interaction between Stat1 and PIASy.
  • PIASy repressed Stat1-mediated gene activation without affecting Stat1's DNA binding.
  • An LXXLL motif in PIASy was found to be essential for its transrepression activity, though not for Stat1 interaction.

Conclusions:

  • PIASy functions as a transcriptional corepressor for Stat1, modulating its activity.
  • The interaction between Stat1 and PIASy is triggered by IFN and leads to repression of gene activation.
  • Distinct PIAS proteins may employ different mechanisms to regulate STAT-mediated gene transcription.

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