NDLI: Inhibition of Stat1-mediated gene activation by PIAS1.

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Inhibition of Stat1-mediated gene activation by PIAS1.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Liu, B. Kushner, S. A. Chung, C. D. Shuai, K. Chang, D. D. Liao, J. Rao, X.
Description	Author Affiliation: Liu B ( Division of Hematology-Oncology, Department of Medicine, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.);
Abstract	STAT (signal transducer and activator of transcription) proteins are latent cytoplasmic transcription factors that become activated by tyrosine phosphorylation in response to cytokine stimulation. Tyrosine phosphorylated STATs dimerize and translocate into the nucleus to activate specific genes. Different members of the STAT protein family have distinct functions in cytokine signaling. Biochemical and genetic analysis has demonstrated that Stat1 is essential for gene activation in response to interferon stimulation. Although progress has been made toward understanding STAT activation, little is known about how STAT signals are down-regulated. We report here the isolation of a family of PIAS (protein inhibitor of activated STAT) proteins. PIAS1, but not other PIAS proteins, blocked the DNA binding activity of Stat1 and inhibited Stat1-mediated gene activation in response to interferon. Coimmunoprecipitation analysis showed that PIAS1 was associated with Stat1 but not Stat2 or Stat3 after ligand stimulation. The in vivo PIAS1-Stat1 interaction requires phosphorylation of Stat1 on Tyr-701. These results identify PIAS1 as a specific inhibitor of Stat1-mediated gene activation and suggest that there may exist a specific PIAS inhibitor in every STAT signaling pathway.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	18
Volume Number	95
Language	English
Publisher	National Academy of Sciences
Publisher Date	1998-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	DNA-Binding Proteins Physiology Gene Expression Regulation Proteins Trans-Activators Amino Acid Sequence Animals Cell Line DNA, Complementary Antagonists & Inhibitors Molecular Sequence Data Phosphorylation Protein Inhibitors Of Activated STAT STAT1 Transcription Factor Sequence Homology, Amino Acid Transcriptional Activation Tyrosine Metabolism Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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