Abstract
Interferon (IFN) treatment induces tyrosine phosphorylation and nuclear translocation of Stat1 (signal transducer and activator of transcription) to activate or repress transcription. We report here that a member of the protein inhibitor of activated STAT family, PIASy, is a transcriptional corepressor of Stat1. IFN treatment triggers the in vivo interaction of Stat1 with PIASy, which represses Stat1-mediated gene activation without blocking the DNA binding activity of Stat1. An LXXLL coregulator signature motif located near the NH(2) terminus of PIASy, although not involved in the PIASy-Stat1 interaction, is required for the transrepression activity of PIASy. Our studies identify PIASy as a transcriptional corepressor of Stat1 and suggest that different PIAS proteins may repress STAT-mediated gene activation through distinct mechanisms.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Binding Sites
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line, Transformed
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Cell Nucleus / metabolism
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DNA / metabolism
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation
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HeLa Cells
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Humans
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Interferon-gamma / pharmacology
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Intracellular Signaling Peptides and Proteins*
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Molecular Sequence Data
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Poly-ADP-Ribose Binding Proteins
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Protein Inhibitors of Activated STAT
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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STAT1 Transcription Factor
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Signal Transduction*
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Trans-Activators / metabolism*
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Transcription, Genetic
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Transcriptional Activation
Substances
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Carrier Proteins
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DNA-Binding Proteins
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Intracellular Signaling Peptides and Proteins
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Nuclear Proteins
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PIAS4 protein, human
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Poly-ADP-Ribose Binding Proteins
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Protein Inhibitors of Activated STAT
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Repressor Proteins
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STAT1 Transcription Factor
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STAT1 protein, human
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Trans-Activators
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Interferon-gamma
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DNA