Cited by 982Cytokine Signaling Pathways and InteractionsGenomics and Chromatin DynamicsPsoriasis: Treatment and Pathogenesis

Specific Inhibition of Stat3 Signal Transduction by PIAS3

Chung, Chan D., Liao, Jiayu, Liu, Bin, Rao, Xiaoping, Jay, Philippe, Berta, Philippe, Shuai, Ke·1997·Science

Abstract

The signal transducer and activator of transcription-3 (Stat3) protein is activated by the interleukin 6 (IL-6) family of cytokines, epidermal growth factor, and leptin. A protein named PIAS3 (protein inhibitor of activated STAT) that binds to Stat3 was isolated and characterized. The association of PIAS3 with Stat3 in vivo was only observed in cells stimulated with ligands that cause the activation of Stat3. PIAS3 blocked the DNA-binding activity of Stat3 and inhibited Stat3-mediated gene activation. Although Stat1 is also phosphorylated in response to IL-6, PIAS3 did not interact with Stat1 or affect its DNA-binding or transcriptional activity. The results indicate that PIAS3 is a specific inhibitor of Stat3.

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Crossref · 10.1126/science.278.5344.1803

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17 of 17 references verified0 citation errors · 0 not checkable

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  • PIAS3 binds specifically to STAT3 and abrogates its activity.

    “Members of the protein inhibitor of activated STAT (PIAS) family, especially PIAS3, are small ubiquitin-like modifier-E3 ligases that bind specifically to STAT3 and abrogate its activity.15”

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Authors
Chung, C. D., Liao, J., Liu, B., Rao, X., Jay, P., Berta, P., & Shuai, K.
Affiliations
University of California, Los Angeles (US)
Corresponding author
  • Chung, Chan D.
  • Liao, Jiayu
  • Shuai, Ke
Venue
Science
Published
1997-12-05
Volume
278
Issue
5344
Pages
1803-1805
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W1993520606
Cited by
980
References
17
Citations by year
2026: 8 · 2025: 10 · 2024: 11 · 2023: 18 · 2022: 21 · 2021: 27 · 2020: 29 · 2019: 26 · 2018: 28 · 2017: 23 · 2016: 26 · 2015: 30 · 2014: 41 · 2013: 47 · 2012: 35
FWCI
18.70
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (1r01ai039612-01)
  • National Cancer Institute (T32CA09056, T32CA009056)
  • National Institute of Allergy and Infectious Diseases (AI39612)
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords
STAT3, PIAS3, signal transduction inhibition, interleukin-6 family cytokines, epidermal growth factor, leptin, STAT1, transcriptional regulation
MeSH terms
Amino Acid Sequence, Animals, Carrier Proteins, Cell Line, DNA, DNA-Binding Proteins, Gene Expression Regulation, Humans, Molecular Sequence Data, Phosphoproteins, Phosphorylation, Recombinant Fusion Proteins, Transfection, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha, Signal Transduction, Transcriptional Activation, Trans-Activators, Interleukin-6, NF-kappa B, Interferon-alpha, Phosphotyrosine, Intracellular Signaling Peptides and Proteins, STAT1 Transcription Factor, STAT3 Transcription Factor, Protein Inhibitors of Activated STAT, Interferon Regulatory Factor-1, Mice

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