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Cited by 166interferon and immune responsesCytokine Signaling Pathways and InteractionsGenomics and Chromatin Dynamics

Recruitment of Stat1 to chromatin is required for interferon-induced serine phosphorylation of Stat1 transactivation domain

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Sadzak, Iwona, Schiff, Melanie, Gattermeier, Irene, Glinitzer, Reingard, Sauer, Ines, Saalmüller, Armin, Yang, Edward, Schaljo, Barbara +1 more·2008·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0801794105PMC PMC2435588
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Abstract

The transcription factor Stat1 plays an essential role in responses to interferons (IFNs). Activation of Stat1 is achieved by phosphorylation on Y701 that is followed by nuclear accumulation. For full transcriptional activity and biological function Stat1 must also be phosphorylated on S727. The molecular mechanisms underlying the IFN-induced S727 phosphorylation are incompletely understood. Here, we show that both Stat1 Y701 phosphorylation and nuclear translocation are required for IFN-induced S727 phosphorylation. We further show that Stat1 mutants lacking the ability to stably associate with chromatin are poorly serine-phosphorylated in response to IFN-γ. The S727 phosphorylation of these mutants is restored on IFN-β treatment that induces the formation of the ISGF3 complex (Stat1/Stat2/Irf9) where Irf9 represents the main DNA binding subunit. These findings indicate that Stat1 needs to be assembled into chromatin-associated transcriptional complexes to become S727-phosphorylated and fully biologically active in response to IFNs. This control mechanism, which may be used by other Stat proteins as well, restricts the final activation step to the chromatin-tethered transcription factor.

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Sorted by citations

Authors
Sadzak, I., Schiff, M., Gattermeier, I., Glinitzer, R., Sauer, I., Saalmüller, A., Yang, E., Schaljo, B., & Kovarik, P.
Affiliations
  • University of Vienna (AT)
  • University of Veterinary Medicine Vienna (AT)
  • Rockefeller University (US)
Corresponding author
Kovarik, Pavel
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2008-07
Volume
105
Issue
26
Pages
8944-8949
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0801794105
PMC
PMC2435588
OpenAlex
W2045575961
Cited by
166
References
2
Citations by year
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FWCI
2.37
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Phaidra (Universität Wien) (submittedVersion, cc-by-nc-nd)
Funders
  • European Commission (ERAS-CT-2003-980409)
  • European Science Foundation (ERAS‐CT‐2003‐980409)
  • Austrian Science Fund (SFB‐F28)
  • European Social Fund (ERAS-CT-2003-980409)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
STAT1, interferon signaling, serine phosphorylation, chromatin association, nuclear translocation, IRF9, STAT2, interferon-gamma, interferon-beta, transcriptional activation
MeSH terms
Animals, Cell Line, Cell Nucleus, Chromatin, Humans, Interferon-gamma, Phosphorylation, Phosphoserine, Protein Binding, Transcriptional Activation, Interferon-beta, Protein Structure, Tertiary, Active Transport, Cell Nucleus, STAT1 Transcription Factor, Mice

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