Activation of the p21(CIP1/WAF1) promoter by bone morphogenetic protein-2 in mouse B lineage cells

Oncogene. 2001 Jul 19;20(32):4383-92. doi: 10.1038/sj.onc.1204572.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism*
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein Receptors
  • Bone Morphogenetic Proteins / pharmacology*
  • COS Cells
  • Cell Lineage
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Hybridomas
  • Mice
  • Oncogene Proteins, Viral / pharmacology
  • Promoter Regions, Genetic*
  • Receptors, Cell Surface / metabolism
  • Receptors, Growth Factor*
  • Repressor Proteins*
  • Response Elements
  • Smad Proteins
  • Smad1 Protein
  • Smad4 Protein
  • Stem Cells / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transfection
  • Transforming Growth Factor beta*


  • BMP2 protein, human
  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA-Binding Proteins
  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Receptors, Cell Surface
  • Receptors, Growth Factor
  • Repressor Proteins
  • Smad Proteins
  • Smad1 Protein
  • Smad1 protein, mouse
  • Smad4 Protein
  • Smad4 protein, mouse
  • Trans-Activators
  • Transforming Growth Factor beta
  • Bone Morphogenetic Protein Receptors