Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

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

Oncogene volume 20, pages 4383–4392 (2001)Cite this article

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  • Attisano L, Wrana JL . 2000 Curr. Opin. Cell Biol. 12: 235–243

  • Bhatia M, Bonnet D, Wu D, Murdoch B, Wrana J, Gallacher L, Dick JE . 1999 J. Exp. Med. 189: 1139–1148

  • Chin YE, Kitagawa M, Su WC, You ZH, Iwamoto Y, Fu XY . 1996 Science 272: 719–722

  • Datto MB, Li Y, Panus JF, Howe DJ, Xiong Y, Wang XF . 1995a Proc. Natl. Acad. Sci. USA 92: 5545–5549

  • Datto MB, Yu Y, Wang XF . 1995b J. Biol. Chem. 270: 28623–28628

  • Dennler S, Itoh S, Vivien D, ten Dijke P, Huet S, Gauthier JM . 1998 EMBO J. 17: 3091–3100

  • Dulic V, Kaufmann WK, Wilson SJ, Tlsty TD, Lees E, Harper JW, Elledge SJ, Reed SI . 1994 Cell 76: 1013–1023

  • El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B . 1993 Cell 75: 817–825

  • El-Deiry WS, Tokino T, Waldman T, Oliner JD, Velculescu VE, Burrell M, Hill DE, Healy E, Rees JL, Hamilton SR, Kinzler KW, Vogelstein B . 1995 Cancer Res. 55: 2910–2919

  • Gross RE, Mehler MF, Mabie PC, Zang Z, Santschi L, Kessler JA . 1996 Neuron 17: 595–606

  • Hogan BLM . 1996 Genes Dev. 10: 1580–1594

  • Imamura T, Takase M, Nishihara A, Oeda E, Hanai J, Kawabata M, Miyazono K . 1997 Nature 389: 622–626

  • Ishida W, Hamamoto T, Kusanagi K, Yagi K, Kawabata M, Takehara K, Sampath TK, Kato M, Miyazono K . 2000 J. Biol. Chem. 275: 6075–6079

  • Ishisaki A, Yamato K, Hashimoto S, Nakao A, Tamaki K, Nonaka K, ten Dijke P, Sugino H, Nishihara T . 1999 J. Biol. Chem. 274: 13637–13642

  • Jernvall J, Aberg T, Kettunen P, Keranen S, Thesleff I . 1998 Development 125: 161–169

  • Jonk LJ, Itoh S, Heldin CH, ten Dijke P, Kruijer W . 1998 J. Biol. Chem. 273: 21145–21152

  • Jost CA, Marin MC, Kaelin Jr WG . 1997 Nature 389: 191–194

  • Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC, Valent A, Minty A, Chalon P, Lelias JM, Dumont X, Ferrara P, McKeon F, Caput D . 1997 Cell 90: 809–819

  • Karim FD, Urness LD, Thummel CS, Klemsz MJ, McKercher SR, Celada A, Van Beveren C, Maki RA, Gunther CV, Nye JA . 1990 Genes Dev. 4: 1451–1453

  • Kawamura C, Kizaki M, Yamato K, Uchida H, Fukuchi Y, Hattori Y, Koseki T, Nishihara T, Ikeda Y . 2000 Blood 96: 2005–2011

  • Kusanagi K, Inoue H, Ishidou Y, Mishima HK, Kawabata M, Miyazono K . 2000 Mol. Biol. Cell 11: 555–565

  • Li JM, Datto MB, Shen X, Hu PP, Yu Y, Wang XF . 1998 Nucleic Acids Res. 26: 2449–2456

  • Liu M, Iavarone A, Freedman LP . 1996a J. Biol. Chem. 271: 31723–31728

  • Liu M, Lee MH, Cohen M, Bommakanti M, Freedman LP . 1996b Genes Dev. 10: 142–153

  • Macleod KF, Sherry N, Hannon G, Beach D, Tokino T, Kinzler K, Vogelstein B, Jacks T . 1995 Genes Dev. 9: 935–944

  • Massague J, Chen YG . 2000 Genes Dev. 14: 627–644

  • Moustakas A, Kardassis D . 1998 Proc. Natl. Acad. Sci. USA 95: 6733–6738

  • Nakao A, Imamura T, Souchelnytskyi S, Kawabata M, Ishisaki A, Oeda E, Tamaki K, Hanai J, Heldin CH, Miyazono K, ten Dijke P . 1997 EMBO J. 16: 5353–5362

  • Nishihara T, Ohsaki Y, Ueda N, Koseki T, Eto Y . 1995 J. Interferon Cytokine Res. 15: 509–516

  • Osada M, Ohba M, Kawahara C, Ishioka C, Kanamaru R, Katoh I, Ikawa Y, Nimura Y, Nakagawara A, Obinata M, Ikawa S . 1998 Nat. Med. 4: 839–843

  • Pardali K, Kurisaki A, Moren A, ten Dijke P, Kardassis D, Moustakas A . 2000 J Biol. Chem. 275: 29244–29256

  • Sherr CJ, Roberts JM . 1999 Genes Dev. 13: 1501–1512

  • Song S, Gulliver GA, Lambert PF . 1998 Proc. Natl. Acad. Sci. USA 95: 2290–2295

  • Tada K, Inoue H, Ebisawa T, Makuuchi M, Kawabata M, Imamura T, Miyazono K . 1999 Genes Cells 4: 731–741

  • ten Dijke P, Miyazono K, Heldin CH . 2000 Trends Biochem. Sci. 25: 64–70

  • Whitman M . 1998 Genes Dev. 12: 2445–2462

  • Wotton D, Lo RS, Lee S, Massague J . 1999 Cell 97: 29–39

  • Yamato K, Hashimoto S, Okahashi N, Ishisaki A, Nonaka K, Kizaki M., Ikeda Y, Nishihara T . 2000 Exp. Cell Res. 257: 198–205

  • Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dotsch V, Andrews NC, Caput D, McKeon F . 1998 Mol. Cell 2: 305–316

  • Zawel L, Dai JL, Buckhaults P, Zhou S, Kinzler KW, Vogelstein B, Kern SE . 1998 Mol. Cell 1: 611–617

  • Zhang Y, Derynck R . 1999 Trends Cell Biol. 9: 274–279

Download references

Acknowledgements

This work was supported in part by grants-in-aid from the Ministry of Education, Science, and Culture of Japan, from the Ministry of Health and Welfare of Japan, and from the Fukuoka Cancer Society, Fukuoka, Japan for cancer research.

Author information

Authors and Affiliations

  1. Division of Oral Health Science, Section of Molecular Cellular Oncology and Microbiology, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8549, Japan

    Kenji Yamato

  2. Department of Oral Science, The National Institute of Infectious Diseases, Tokyo, 162-8640, Japan

    Shinichi Hashimoto, Nobuo Okahashi & Takeyoshi Koseki

  3. Department of Biochemistry, The Cancer Institute (JFCR), Tokyo, 170-8455, Japan

    Takeshi Imamura & Kohei Miyazono

  4. Division of Hematology, Keio University, School of Medicine, Tokyo, 160-8582, Japan

    Hideo Uchida, Masahiro Kizaki & Yasuo Ikeda

  5. Biosignaling Department, The National Institute of Bioscience and Human Technology, Tsukuba, 305-8566, Japan

    Akira Ishisaki

  6. Department of Oral Microbiology, Kyushu Dental College, Fukuoka, 803-8580, Japan

    Tatsuji Nishihara

Authors
  1. Kenji Yamato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shinichi Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takeshi Imamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hideo Uchida
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nobuo Okahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takeyoshi Koseki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Akira Ishisaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Masahiro Kizaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kohei Miyazono
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yasuo Ikeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Tatsuji Nishihara
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yamato, K., Hashimoto, S., Imamura, T. et al. Activation of the p21CIP1/WAF1 promoter by bone morphogenetic protein-2 in mouse B lineage cells. Oncogene 20, 4383–4392 (2001). https://doi.org/10.1038/sj.onc.1204572

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204572

Keywords

This article is cited by

Search

Advanced search

Quick links