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

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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

DOI 10.1126/science.278.5344.1803

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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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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
ORCID: Liao, Jiayu
Liu, Bin
Jay, Philippe
Shuai, Ke
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1997-12-05
Volume: 278
Issue: 5344
Pages: 1803-1805
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.278.5344.1803
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: Life Sciences › Immunology and Microbiology › Immunology › 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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Specific Inhibition of Stat3 Signal Transduction by PIAS3

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