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GOOSECOID inhibits erythrocyte differentiation by competing with Rb for PU.1 binding in murine cells

Oncogene volume 18, pages 6795–6805 (1999)Cite this article

Abstract

Misexpression of the dorsal mesodermal patterning factor goosecoid on the ventral side of amphibian embryos results in inhibition of blood formation in early embryogenesis. To investigate the mechanism of this inhibition, we ectopically expressed goosecoid in erythroleukemia cells. While erythroid differentiation of these cells can be induced by activin, goosecoid expressing cells were unresponsive to activin. We demonstrate an in vitro interaction between the oncogene PU.1, an ets family transcription factor thought to play a role in erythropoiesis, and the goosecoid protein (GSC). Interaction with PU.1 was specific as GSC did not bind to the ets family members, Fli-1 or Ets-2. The ability of goosecoid expressing erythroleukemia cells to differentiate in response to activin was rescued by coexpression of the GSC-binding N-terminal portion of PU.1. The N-terminal portion of PU.1 was co-immunoprecipitated with anti-GSC antibodies as well. The N-terminal domain of PU.1 is the region recognized by the retinoblastoma protein (Rb), a tumor suppressor gene presumably involved in erythroid differentiation. We show that GSC competitively inhibits binding of Rb to PU.1. Our data suggest that the suppression of blood formation by GSC could, at least in part, be mediated by binding to PU.1.

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References

  • Aplan PD, Nakahara K, Orkin SH and Kirsch IR. . 1992 EMBO J. 11: 4073–4081.

  • Begley CG, Aplan PD, Denning SM, Haynes BF, Waldmann TA, et al. 1989 Proc. Natl. Acad. Sci. USA 86: 10128–10132.

  • Ben-David Y, Giddens EB, Letwin K and Bernstein A. . 1991 Genes Dev. 5: 908–918.

  • Bernards R, Schackleford GM, Gerber MR, Horowitz JM, Friend SH, et al. 1989 Proc. Natl. Acad. Sci. USA 86: 6474–6478.

  • Blum M, Gaunt SJ, Cho KWY, Steinbeisser H, Blumberg B, et al. 1992 Cell 69: 1097–1106.

  • Blumberg B, Wright CVE, De Robertis EM and Cho KWY. . 1991 Science 253: 194–196.

  • Chellappan SP, Hiebert S, Mudryl M, Horowitz JM and Nevins JR. . 1991 Cell 65: 1053–1061.

  • Cho KWY, Blumberg B, Steinbeisser H and De Robertis EM. . 1991 Cell 67: 1111–1120.

  • Clarke AR, Maandag ER, van Roon M, van der Lugt NM T, van der Valk, et al. 1992 Nature 359: 328–330.

  • De Robertis EM, Blum M, Niehrs C and Steinbeisser H. . 1992 Development (Suppl.) 167–171.

  • Dowdy SF, Hinds PW, Louie K, Reed SI, Arnold A, et al. 1993 Cell 73: 499–511.

  • Eto Y, Tsuji T, Takezawa M, Takeno S, Yokogawa Y, et al. 1987 Biochem. Biophys. Res. Commun. 142: 1095–1103.

  • Goldfarb AN, Goueli S, Mikelson D and Greenberg JM. . 1992 Blood 80: 2858–2866.

  • Gu W, Schneider JW, Condorelli G, Kaushal S, Mahdavi V, et al. 1993 Cell 72: 309–324.

  • Guan K and Dixon JE. . 1991 Anal. Biochem. 192: 262–267.

  • Hagemeier C, Bannister AJ, Cook A and Kouzarides T. . 1993 Proc. Natl. Sci. Acad. USA 90: 1580–1584.

  • Hromas R, Orazi A, Neiman RS, Maki R, Beveran CV, et al. 1993 Blood 82: 2998–3004.

  • Ikawa Y, Aida M and Inoue Y. . 1976 Gann 67: 767–770.

  • Jacks T, Fazeli A, Schmitt EM, Bronson RT, Goodell MA, et al. 1992 Nature 359: 295–300.

  • Klemsz MJ, McKercher SR, Celada A, Beveren CV and Maki RA. . 1990 Cell 61: 113–124.

  • Klemsz MJ and Maki RA. . 1997 Mol. Cell. Biol. 16: 390–397.

  • Kulessa H, Frampton J and Graf T. . 1995 Genes Dev. 9: 1250–1262.

  • Lee EY-HP, Chang C-Y, Hu N, Wang Y-C J, Lai C-C, et al. 1992 Nature 359: 288–294.

  • Matsushime H, Ewen ME, Strom DK, Kato J-Y, Hanks SK, et al. 1992 Cell 71: 323–334.

  • McKercher SC, Torbett BE, Anderson KL, Henkel GW, Vestal DJ, et al. 1996 EMBO J. 15: 5647–5658.

  • Melton DA, Krieg PA, Rebagliati MR, Maniatis T, Zinn K, et al. 1984 Nucleic Acids Res. 12: 7035–7056.

  • Moreau-Gachelin F, Wendling F, Molina T, Denis N, Titeux M, et al. 1996 Mol. Cell. Biol. 16: 2453–2463.

  • Niehrs C, Keller NR, Cho KWY and De Robertis EM. . 1993 Cell 72: 491–503.

  • Niehrs C, Steinbeisser H and De Robertis EM. . 1994 Science 263: 817–820.

  • Rao G, Rekhtman N, Cheng G, Krasikov T and Skoultchi AI. . 1997 Oncogene 14: 123–127.

  • Scott EW, Simon MC, Anastasi J and Singh H. . 1994 Science 265: 1573–1577.

  • Scott EW, Fisher RC, Olson MC, Kehrli EW, Simon MC, et al. 1997 Immunity 6: 437–447.

  • Schuetze S, Paul R, Gliniak BC and Kabat D. . 1992 Mol. Cell. Biol. 12: 2967–2975.

  • Schuetze S, Stenberg PE and Kabat D. . 1993 Mol. Cell. Biol. 13: 5670–5678.

  • Shivdasani RA and Orkin SH. . 1996 Blood 87: 4025–4039.

  • Spemann H and Mangold H. . 1924 Foundations of Experimental Embryology. Willer BH and Oppenheimer JM. (eds). Hafner: New York pp. 144–184.

    Google Scholar 

  • Tsai SF, Strauss E and Orkin SH. . 1991 Genes Dev. 5: 919–931.

  • Tsai FY, Keller G, Kuo FC, Weiss MJ, Chen J-Z, et al. 1994 Nature 371: 221–226.

  • Watson DK, McWilliams MJ, Lapis P, Lautenberger JA, Schweinfest CW, et al. 1988 Proc. Natl. Acad. Sci. USA. 85: 7862–7866.

  • Whyte P, Buchkovich KJ, Horowitz JM, Friend SH, Raybuck M, et al. 1988 Nature 334: 124–129.

  • Yamada T, Kondoh N, Matsumoto M, Yoshida M, Maekawa A, et al. 1997 Blood 89: 1383–1393.

  • Yu J, Shao L-E, Lemas V, Yu AL, Vaughan J, et al. 1987 Nature 330: 765–767.

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Acknowledgements

We are grateful to Dr Yuzuru Eto for the generous supply of activin and F5-5 cells. We are also grateful to Dr Robert Weinberg for the generous supply of mouse Rb gene and Drs Dennis Templeton and Masanori Hatakeyama for information about Rb. We appreciate the continuous encouragement of Drs Tomio Tada, Toshio Kuroki, the former president of Kochi Medical School, Isamu Kitamura and the president of Kochi Medical School, Hisao Ikeda. We also appreciate Daniel B Ribble for critical reading of this manuscript. This work was supported in part by Grants-in-Aid for Scientific Research and Grants-in-Aid for Special Project Research, Cancer Biology, from the Japanese Ministry of Education, Science, and Culture and also supported by Kochi Medical School President Research Fund.

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Authors and Affiliations

  1. Medical Research Center, Kochi Medical School, Kohasu, Okoh-cho, Nankoku City, 783-8505, Kochi, Japan

    Yuko Konishi & Akira Tominaga

  2. Medical Biology, Kochi Medical School, Kohasu, Okoh-cho, Nankoku City, 783-8505, Kochi, Japan

    Mari Tominaga, Yoshiya Watanabe & Akira Tominaga

  3. Division of Pulmonary Disease, Kumamoto City Hospital, Koto, Kumamoto City, 862-0808, Kumamoto, Japan

    Fumiya Imamura

  4. Division of Pulmonary Disease, Kumamoto City Hospital, Koto, Kumamoto City, 862-0808, Kumamoto, Japan

    Adam Goldfarb

  5. The Burnham Institute, La Jolla, 92037, California, CA, USA

    Richard Maki

  6. Forschungszentrum Karlsruhe, Institute of Genetics, PO Box 3640, D-76021, Karlsruhe, Germany

    Martin Blum

  7. HHMI and Department of Biological Chemistry, University of California, School of Medicine, Los Angeles, 90095-1662, California, CA, USA

    Eddy M De Robertis

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  1. Yuko Konishi
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Konishi, Y., Tominaga, M., Watanabe, Y. et al. GOOSECOID inhibits erythrocyte differentiation by competing with Rb for PU.1 binding in murine cells. Oncogene 18, 6795–6805 (1999). https://doi.org/10.1038/sj.onc.1203118

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