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PMID: 9388184 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Specific inhibition of Stat3 signal transduction by PIAS3.

Science (New York, N.Y.) ·Vol. 278 ·No. 5344 ·1997-12-05 ·Pages 1803-5

Chung CD, Liao J, Liu B, Rao X, Jay P, Berta P, Shuai K

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.

MeSH Terms

Amino Acid Sequence Animals Carrier Proteins/chemistry,genetics,metabolism,pharmacology Cell Line DNA/metabolism DNA-Binding Proteins/genetics,metabolism Gene Expression Regulation Humans Interferon Regulatory Factor-1 Interferon-alpha/pharmacology Interleukin-6/pharmacology Intracellular Signaling Peptides and Proteins Mice Molecular Sequence Data NF-kappa B/metabolism Phosphoproteins/genetics Phosphorylation Phosphotyrosine/metabolism Protein Inhibitors of Activated STAT Recombinant Fusion Proteins/pharmacology STAT1 Transcription Factor STAT3 Transcription Factor Signal Transduction Trans-Activators/metabolism Transcriptional Activation Transfection Tumor Cells, Cultured Tumor Necrosis Factor-alpha/pharmacology

Chemicals

Carrier Proteins DNA-Binding Proteins IRF1 protein, human Interferon Regulatory Factor-1 Interferon-alpha Interleukin-6 Intracellular Signaling Peptides and Proteins Irf1 protein, mouse NF-kappa B Phosphoproteins Pias3 protein, mouse Protein Inhibitors of Activated STAT Recombinant Fusion Proteins STAT1 Transcription Factor STAT1 protein, human STAT3 Transcription Factor STAT3 protein, human Stat1 protein, mouse Stat3 protein, mouse Trans-Activators Tumor Necrosis Factor-alpha Phosphotyrosine DNA

Authors & Affiliations

7 authors, click to expand affiliations / ORCID

Chung C D

Department of Biological Chemistry, University of California, Los Angeles, CA 90095, USA.

Liao J

Liu B

Rao X

Jay P

Berta P

Shuai K

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

0036-8075

DOI

10.1126/science.278.5344.1803

Published

1997-12-05

Pages

1803-5

Language

English

Region

United States

NLM ID

0404511

Subset

Grants

NIAID NIH HHS · AI39612 · United States

NCI NIH HHS · T32CA09056 · United States

Databases

GENBANK

H58757

External Links

PubMed source DOI: 10.1126/science.278.5344.1803 View journal details

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Specific inhibition of Stat3 signal transduction by PIAS3.

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