Activation of the p21(CIP1/WAF1) promoter by bone morphogenetic protein-2 in mouse B lineage cells.
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.
Yamato
K
K
Section of Molecular Cellular Oncology and Microbiology, Division of Oral Health Science, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8549, Japan.
Hashimoto
S
S
Imamura
T
T
Uchida
H
H
Okahashi
N
N
Koseki
T
T
Ishisaki
A
A
Kizaki
M
M
Miyazono
K
K
Ikeda
Y
Y
Nishihara
T
T
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D055396:Bone Morphogenetic Protein 2; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D019556:COS Cells; D019070:Cell Lineage; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006825:Hybridomas; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000378:metabolism; D017978:Receptors, Growth Factor; D012097:Repressor Proteins; D020218:Response Elements; D051785:Smad Proteins; D051898:Smad1 Protein; D051901:Smad4 Protein; D013234:Stem Cells / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D012097:Repressor Proteins; D051785:Smad Proteins; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D052004:Bone Morphogenetic Protein Receptors