Abstract
Serine-threonine kinase receptor-associated protein (STRAP) functions as a regulator of both TGF-β and p53 signaling. However, the regulatory mechanism of STRAP activity is not understood. In this study, we report that B-MYB is a new STRAP-interacting protein, and that an amino-terminal DNA-binding domain and an area (amino acids 373-468) between the acidic and conserved regions of B-MYB mediate the B-MYB·STRAP interaction. Functionally, B-MYB enhances STRAP-mediated inhibition of TGF-β signaling pathways, such as apoptosis and growth inhibition, by modulating complex formation between the TGF-β receptor and SMAD3 or SMAD7. Furthermore, coexpression of B-MYB results in a dose-dependent increase in STRAP-mediated stimulation of p53-induced apoptosis and cell cycle arrest via direct interaction. Confocal microscopy showed that B-MYB prevents the normal translocation of SMAD3 in response to TGF-β1 and stimulates p53 nuclear translocation. These results suggest that B-MYB acts as a positive regulator of STRAP.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / physiology*
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Breast Neoplasms
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Cell Cycle Proteins / chemistry
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Nucleus / metabolism
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Female
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HCT116 Cells
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HEK293 Cells
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HeLa Cells
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Hep G2 Cells
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Humans
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / metabolism*
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Protein Structure, Tertiary
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Proto-Oncogene Proteins c-mdm2 / metabolism
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RNA, Small Interfering
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RNA-Binding Proteins
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Receptors, Transforming Growth Factor beta / metabolism
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Signal Transduction / physiology*
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Smad3 Protein / metabolism
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Smad7 Protein / metabolism
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Trans-Activators / chemistry
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transforming Growth Factor beta / metabolism
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism
Substances
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Cell Cycle Proteins
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MYBL2 protein, human
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Neoplasm Proteins
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RNA, Small Interfering
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RNA-Binding Proteins
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Receptors, Transforming Growth Factor beta
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SMAD3 protein, human
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SMAD7 protein, human
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STRAP protein, human
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Smad3 Protein
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Smad7 Protein
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TP53 protein, human
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Trans-Activators
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Transforming Growth Factor beta
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Tumor Suppressor Protein p53
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MDM2 protein, human
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Proto-Oncogene Proteins c-mdm2