Abstract
BMPs exert a negative growth effect on various types of cells. We have previously reported that BMP-2 inhibited the growth of HS-72 mouse hybridoma cells by inducing p21(CIP1/WAF1) expression. In the present study, we demonstrated that BMP-2 activated the mouse p21(CIP1/WAF1) promoter in HS-72 cells, and that a 29-base pair (b) region of the promoter (-1928/-1900 relative to the TATA box), conserved between mice and humans, was responsive to BMP-2 as well as expression of Smad1, Smad4, and constitutively active mutants of BMP type I receptors. Furthermore, an oligonucleotide containing the 29-b region was found to be associated with Smad4 and phosphorylated Smad1 in the nuclear extract of BMP-2-stimulated HS-72 cells. These results suggested that BMP-2 might activate p21(CIP1/WAF1) transcription by inducing a binding of Smad4 and Smad1 to the 29-b region in HS-72 cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocytes / metabolism*
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Protein Receptors
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Bone Morphogenetic Proteins / pharmacology*
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COS Cells
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Cell Lineage
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / genetics*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Hybridomas
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Mice
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Oncogene Proteins, Viral / pharmacology
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Promoter Regions, Genetic*
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Receptors, Cell Surface / metabolism
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Receptors, Growth Factor*
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Repressor Proteins*
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Response Elements
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Smad Proteins
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Smad1 Protein
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Smad4 Protein
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Stem Cells / metabolism
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Trans-Activators / genetics
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Trans-Activators / metabolism
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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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Bmp2 protein, mouse
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins
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Cdkn1a protein, mouse
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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DNA-Binding Proteins
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E6 protein, Human papillomavirus type 16
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Oncogene Proteins, Viral
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Receptors, Cell Surface
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Receptors, Growth Factor
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Repressor Proteins
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Smad Proteins
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Smad1 Protein
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Smad1 protein, mouse
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Smad4 Protein
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Smad4 protein, mouse
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Trans-Activators
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Transforming Growth Factor beta
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Bone Morphogenetic Protein Receptors