Abstract
Smad proteins transduce signals from transforming growth factor-beta (TGF-beta) superfamily ligands that regulate cell proliferation, differentiation and death through activation of receptor serine/threonine kinases. Phosphorylation of receptor-activated Smads (R-Smads) leads to formation of complexes with the common mediator Smad (Co-Smad), which are imported to the nucleus. Nuclear Smad oligomers bind to DNA and associate with transcription factors to regulate expression of target genes. Alternatively, nuclear R-Smads associate with ubiquitin ligases and promote degradation of transcriptional repressors, thus facilitating target gene regulation by TGF-beta. Smads themselves can also become ubiquitinated and are degraded by proteasomes. Finally, the inhibitory Smads (I-Smads) block phosphorylation of R-Smads by the receptors and promote ubiquitination and degradation of receptor complexes, thus inhibiting signalling.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Activin Receptors, Type I / metabolism*
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Activin Receptors, Type I / physiology
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Animals
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DNA-Binding Proteins / physiology
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Humans
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Phosphoproteins / physiology
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Protein Serine-Threonine Kinases
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Receptor Protein-Tyrosine Kinases / metabolism*
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Receptor Protein-Tyrosine Kinases / physiology
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Receptor, Transforming Growth Factor-beta Type I
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Receptor, Transforming Growth Factor-beta Type II
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Receptors, Transforming Growth Factor beta / metabolism*
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Receptors, Transforming Growth Factor beta / physiology
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Signal Transduction / physiology*
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Smad Proteins
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Smad2 Protein
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Smad3 Protein
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Smad4 Protein
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Smad5 Protein
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Smad8 Protein
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Trans-Activators / physiology
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Transforming Growth Factor beta / physiology*
Substances
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DNA-Binding Proteins
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Phosphoproteins
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Receptors, Transforming Growth Factor beta
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SMAD2 protein, human
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SMAD3 protein, human
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SMAD4 protein, human
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SMAD5 protein, human
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SMAD9 protein, human
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Smad Proteins
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Smad2 Protein
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Smad3 Protein
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Smad4 Protein
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Smad4 protein, rat
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Smad5 Protein
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Smad8 Protein
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Trans-Activators
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Transforming Growth Factor beta
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Receptor Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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Activin Receptors, Type I
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Receptor, Transforming Growth Factor-beta Type I
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Receptor, Transforming Growth Factor-beta Type II
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Tgfbr1 protein, rat