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Transcriptional cross-regulation of RUNX1 by RUNX3 in human B cells

Oncogene volume 24, pages 1873–1881 (2005)Cite this article

Abstract

RUNX transcription factors are important in development and in numerous types of human cancer. They act as either transcriptional activators or repressors and can be proto-oncogenes or tumour suppressors. Understanding their regulation and interaction may explain how RUNX factors contribute to such different and often opposing biological processes. We show that RUNX3 regulates RUNX1 expression, contributing to the mutually exclusive expression of RUNX3 and RUNX1 in human B lymphoid cell lines. RUNX3 repressed the RUNX1 P1 promoter by binding specifically to conserved RUNX sites near the transcription start of the promoter. siRNA inhibition of RUNX3 in lymphoblastoid cells resulted in increased RUNX1 expression, indicating that continuous expression of physiological levels of RUNX3 is required to maintain repression. Furthermore, expression of RUNX3 was required for efficient proliferation of B cells immortalized by Epstein–Barr virus. Cross-regulation between different RUNX family members is therefore a means of controlling RUNX protein expression and must now be considered in the interpretation of pathological changes due to loss of RUNX3 tumour suppressor function or following gene duplication or translocation events.

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References

  • Aronson BD, Fisher AL, Blechman K, Caudy M and Gergen JP . (1997). Mol. Cell Biol., 17, 5581–5587.

  • Bangsow C, Rubins N, Glusman G, Bernstein Y, Negreanu V, Goldenberg D, Lotem J, Ben-Asher E, Lancet D, Levanon D and Groner Y . (2001). Gene, 279, 221–232.

  • Ben-Bassat H, Goldblum N, Mitrani S, Goldblum T, Yoffey JM, Cohen MM, Bentwich Z, Ramot B, Klein E and Klein G . (1977). Int. J. Cancer, 19, 27–33.

  • Bernardin F, Yang Y, Civin CI and Friedman AD . (2002). Cancer Biol. Ther., 1, 492–496.

  • Brimmell M, Mendiola R, Mangion J and Packham G . (1998). Oncogene, 16, 1803–1812.

  • Brummelkamp TR, Bernards R and Agami R . (2002). Science, 296, 550–553.

  • Cameron ER and Neil JC . (2004). Oncogene, 23, 4308–4314.

  • Drissi H, Luc Q, Shakoori R, Chuva De Sousa Lopes S, Choi JY, Terry A, Hu M, Jones S, Neil JC, Lian JB, Stein JL, Van Wijnen AJ and Stein GS . (2000). J. Cell Physiol., 184, 341–350.

  • Durst KL and Hiebert SW . (2004). Oncogene, 23, 4220–4224.

  • Fainaru O, Woolf E, Lotem J, Yarmus M, Brenner O, Goldenberg D, Negreanu V, Bernstein Y, Levanon D, Jung S and Groner Y . (2004). EMBO J., 23, 969–979.

  • Fujita T, Azuma Y, Fukuyama R, Hattori Y, Yoshida C, Koida M, Ogita K and Komori T . (2004). J. Cell Biol., 166, 85–95.

  • Ghozi MC, Bernstein Y, Negreanu V, Levanon D and Groner Y . (1996). Proc. Natl. Acad. Sci. USA, 93, 1935–1940.

  • Guo WH, Weng LQ, Ito K, Chen LF, Nakanishi H, Tatematsu M and Ito Y . (2002). Oncogene, 21, 8351–8355.

  • Hofelmayr H, Strobl LJ, Marschall G, Bornkamm GW and Zimber-Strobl U . (2001). J. Virol., 75, 2033–2040.

  • Hofelmayr H, Strobl LJ, Stein C, Laux G, Marschall G, Bornkamm GW and Zimber-Strobl U . (1999). J. Virol., 73, 2770–2780.

  • Huang G, Shigesada K, Ito K, Wee HJ, Yokomizo T and Ito Y . (2001). EMBO J., 20, 723–733.

  • Ichikawa M, Asai T, Saito T, Yamamoto G, Seo S, Yamazaki I, Yamagata T, Mitani K, Chiba S, Hirai H, Ogawa S and Kurokawa M . (2004). Nat. Med., 10, 299–304.

  • Inoue K, Ozaki S, Shiga T, Ito K, Masuda T, Okado N, Iseda T, Kawaguchi S, Ogawa M, Bae SC, Yamashita N, Itohara S, Kudo N and Ito Y . (2002). Nat. Neurosci., 5, 946–954.

  • Javed A, Guo B, Hiebert S, Choi JY, Green J, Zhao SC, Osborne MA, Stifani S, Stein JL, Lian JB, van Wijnen AJ and Stein GS . (2000). J. Cell Sci., 113 (Part 12), 2221–2231.

  • Kato N, Tamura G, Fukase M, Shibuya H and Motoyama T . (2003). Am. J. Pathol., 163, 387–391.

  • Kempkes B, Spitkovsky D, Jansen-Durr P, Ellwart JW, Kremmer E, Delecluse HJ, Rottenberger C, Bornkamm GW and Hammerschmidt W . (1995). EMBO J., 14, 88–96.

  • Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S and Kishimoto T . (1997). Cell, 89, 755–764.

  • Lacaud G, Gore L, Kennedy M, Kouskoff V, Kingsley P, Hogan C, Carlsson L, Speck N, Palis J and Keller G . (2002). Blood, 100, 458–466.

  • Lebestky T, Jung SH and Banerjee U . (2003). Genes Dev., 17, 348–353.

  • Levanon D, Bettoun D, Harris-Cerruti C, Woolf E, Negreanu V, Eilam R, Bernstein Y, Goldenberg D, Xiao C, Fliegauf M, Kremer E, Otto F, Brenner O, Lev-Tov A and Groner Y . (2002). EMBO J., 21, 3454–3463.

  • Levanon D, Brenner O, Negreanu V, Bettoun D, Woolf E, Eilam R, Lotem J, Gat U, Otto F, Speck N and Groner Y . (2001). Mech. Dev., 109, 413–417.

  • Levanon D, Goldstein RE, Bernstein Y, Tang H, Goldenberg D, Stifani S, Paroush Z and Groner Y . (1998). Proc. Natl. Acad. Sci. USA, 95, 11590–11595.

  • Levanon D, Negreanu V, Bernstein Y, Bar-Am I, Avivi L and Groner Y . (1994). Genomics, 23, 425–432.

  • Li QL, Ito K, Sakakura C, Fukamachi H, Inoue K, Chi XZ, Lee KY, Nomura S, Lee CW, Han SB, Kim HM, Kim WJ, Yamamoto H, Yamashita N, Yano T, Ikeda T, Itohara S, Inazawa J, Abe T, Hagiwara A, Yamagishi H, Ooe A, Kaneda A, Sugimura T, Ushijima T, Bae SC and Ito Y . (2002). Cell, 109, 113–124.

  • Lutterbach B, Westendorf JJ, Linggi B, Isaac S, Seto E and Hiebert SW . (2000). J. Biol. Chem., 275, 651–656.

  • Mann KP, Staunton D and Thorley-Lawson DA . (1985). J. Virol., 55, 710–720.

  • Martensson A, Xie XQ, Persson C, Holm M, Grundstrom T and Martensson IL . (2001). Eur. J. Immunol., 31, 3165–3174.

  • Miyoshi H, Ohira M, Shimizu K, Mitani K, Hirai H, Imai T, Yokoyama K, Soeda E and Ohki M . (1995). Nucleic Acids Res., 23, 2762–2769.

  • Miyoshi H, Shimizu K, Kozu T, Maseki N, Kaneko Y and Ohki M . (1991). Proc. Natl. Acad. Sci. USA, 88, 10431–10434.

  • Okuda T, van Deursen J, Hiebert SW, Grosveld G and Downing JR . (1996). Cell, 84, 321–330.

  • Rini D and Calabi F . (2001). Gene, 273, 13–22.

  • Shi MJ and Stavnezer J . (1998). J. Immunol., 161, 6751–6760.

  • Spender L, Cannell E, Hollyoake M, Wensing B, Gawn J, Brimmell M, Packham G and Farrell P . (1999). J. Virol., 73, 4678–4688.

  • Spender LC, Cornish GH, Sullivan A and Farrell PJ . (2002). J. Virol., 76, 4919–4927.

  • Strobl LJ, Hofelmayr H, Marschall G, Brielmeier M, Bornkamm GW and Zimber-Strobl U . (2000). J. Virol., 74, 1727–1735.

  • Strobl LJ, Hofelmayr H, Stein C, Marschall G, Brielmeier M, Laux G, Bornkamm GW and Zimber-Strobl U . (1997). Immunobiology, 198, 299–306.

  • Taniuchi I, Osato M, Egawa T, Sunshine MJ, Bae SC, Komori T, Ito Y and Littman DR . (2002). Cell, 111, 621–633.

  • Wada M, Yazumi S, Takaishi S, Hasegawa K, Sawada M, Tanaka H, Ida H, Sakakura C, Ito K, Ito Y and Chiba T . (2004). Oncogene, 23, 2401–2407.

  • Woolf E, Xiao C, Fainaru O, Lotem J, Rosen D, Negreanu V, Bernstein Y, Goldenberg D, Brenner O, Berke G, Levanon D and Groner Y . (2003). Proc. Natl. Acad. Sci. USA, 100, 7731–7736.

  • Wotton S, Stewart M, Blyth K, Vaillant F, Kilbey A, Neil JC and Cameron ER . (2002). Cancer Res., 62, 7181–7185.

  • Xiao WH and Liu WW . (2004). World J Gastroenterol., 10, 376–380.

  • Yoshida CA, Yamamoto H, Fujita T, Furuichi T, Ito K, Inoue K, Yamana K, Zanma A, Takada K, Ito Y and Komori T . (2004). Genes Dev., 18, 952–963.

  • Zhang DE, Hetherington CJ, Meyers S, Rhoades KL, Larson CJ, Chen HM, Hiebert SW and Tenen DG . (1996). Mol. Cell Biol., 16, 1231–1240.

  • Zhang Y and Derynck R . (2000). J. Biol. Chem., 275, 16979–16985.

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Author notes

  1. Lindsay C Spender

    Present address: The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK

  2. Lindsay C Spender and Hannah J Whiteman: These authors contributed equally to the work

Authors and Affiliations

  1. Department of Virology, Ludwig Institute for Cancer Research, Imperial College Faculty of Medicine, Norfork Place, St Mary's Campus, Norfolk Place, London, W2 1PG, UK

    Lindsay C Spender, Hannah J Whiteman, Claudio Elgueta Karstegl & Paul J Farrell

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  1. Lindsay C Spender
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Correspondence to Paul J Farrell.

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Spender, L., Whiteman, H., Karstegl, C. et al. Transcriptional cross-regulation of RUNX1 by RUNX3 in human B cells. Oncogene 24, 1873–1881 (2005). https://doi.org/10.1038/sj.onc.1208404

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