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 prev iously reported that BMP-2 inhibited the growth of HS-72 mouse hybridoma ce lls by inducing p21(CIP1/WAF1) expression. In the present study, we demonst rated that BMP-2 activated the mouse p21(CIP1/WAF1) promoter in MS-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 suggeste d that BMP-2 might activate p21(CIP1/WAF1) transcription by inducing a bind ing of Smad4 and Smad1 to the 29-b region in HS-72 cells.