Specific Inhibition of Stat3 Signal Transduction by PIAS3

Author:

Chung Chan D.1234,Liao Jiayu1234,Liu Bin1234,Rao Xiaoping1234,Jay Philippe1234,Berta Philippe1234,Shuai Ke1234

Affiliation:

1. C. D. Chung and J. Liao, Department of Biological Chemistry, University of California, Los Angeles, CA 90095, USA.

2. B. Liu and X. Rao, Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles, CA 90095, USA.

3. P. Jay and P. Berta, Centre de Recherche de Biochimie Macromoleculaire, 1919 route de Mende, 34000 Montpellier, France.

4. K. Shuai, Division of Hematology-Oncology, Department of Medicine; Department of Biological Chemistry; and Molecular Biology Institute, University of California, 11-934 Factor Building, 10833 LeConte Avenue, Los Angeles, CA 90095–1678, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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