Abstract
Bone morphogenetic proteins (BMPs) play central roles in differentiation, development, and physiologic tissue remodeling. Recently, we have demonstrated that a protein inhibitor of activated STAT, PIASy, suppresses TGF-beta signaling by interacting with Sma and MAD-related protein 3 (Smad3). In this study, we examined a PIASy-dependent inhibitory effect on BMP signaling. PIASy expression was induced by BMP-2 stimulation and suppressed BMP-2-dependent Smad activity in hepatoma cells. Furthermore, BMP-2-regulated Smads directly bound to PIASy. We also demonstrated that the RING domain of PIASy played an important role in PIASy-mediated suppression of Smad activity. We here provide evidence that the inhibitory action of PIASy on BMP-regulated Smad activity was due to direct physical interactions between Smads and PIASy through its RING domain.
MeSH terms
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Blotting, Northern
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins / chemistry*
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Bone Morphogenetic Proteins / metabolism
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Carcinoma, Hepatocellular / metabolism
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Carrier Proteins / chemistry*
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Cell Line
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation
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Humans
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Immunoblotting
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Intracellular Signaling Peptides and Proteins*
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Luciferases / metabolism
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Poly-ADP-Ribose Binding Proteins
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Precipitin Tests
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Protein Binding
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Protein Inhibitors of Activated STAT
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Protein Structure, Tertiary
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction*
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Smad Proteins
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Time Factors
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Trans-Activators / metabolism
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Transcription, Genetic
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Transfection
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Transforming Growth Factor beta*
Substances
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BMP2 protein, human
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins
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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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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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Smad Proteins
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Trans-Activators
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Transforming Growth Factor beta
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Luciferases