Activation of the p21CIP1/WAF1 promoter by bone morphogenetic protein-2 in mouse B lineage cells

Kenji Yamato, Shinichi Hashimoto, Takeshi Imamura, Hideo Uchida, Nobuo Okahashi, Takeyoshi Koseki, Akira Ishisaki, Masahiro Kizaki, Kohei Miyazono, Yasuo Ikeda, Tatsuji Nishihara

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19 Citations (Scopus)

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 p21CIP1/WAF1 expression. In the present study, we demonstrated that BMP-2 activated the mouse p21CIP1/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 p21CIP1/WAF1 transcription by inducing a binding of Smad4 and Smad1 to the 29-b region in HS-72 cells.

Original languageEnglish
Pages (from-to)4383-4392
Number of pages10
JournalOncogene
Volume20
Issue number32
DOIs
Publication statusPublished - 2001 Jul 19
Externally publishedYes

Keywords

  • BMP
  • P21
  • Promoter
  • Smad
  • Transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Yamato, K., Hashimoto, S., Imamura, T., Uchida, H., Okahashi, N., Koseki, T., Ishisaki, A., Kizaki, M., Miyazono, K., Ikeda, Y., & Nishihara, T. (2001). Activation of the p21CIP1/WAF1 promoter by bone morphogenetic protein-2 in mouse B lineage cells. Oncogene, 20(32), 4383-4392. https://doi.org/10.1038/sj.onc.1204572