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:

The DNA binding activity of TAL-1 is not required to induce leukemia/lymphoma in mice

Oncogene volume 20, pages 3897–3905 (2001)Cite this article

Abstract

Activation of the basic helix–loop–helix (bHLH) gene TAL-1 (or SCL) is the most frequent gain-of-function mutation in pediatric T cell acute lymphoblastic leukemia (T-ALL). Similarly, mis-expression of tal-1 in the thymus of transgenic mice results in the development of clonal T cell lymphoblastic leukemia. To determine the mechanism(s) of tal-1-induced leukemogenesis, we created transgenic mice expressing a DNA binding mutant of tal-1. Surprisingly, these mice develop disease, demonstrating that the DNA binding properties of tal-1 are not required to induce leukemia/lymphoma in mice. However, wild type tal-1 and the DNA binding mutant both form stable complexes with E2A proteins. In addition, tal-1 stimulates differentiation of CD8-single positive thymocytes but inhibits the development of CD4-single positive cells: effects also observed in E2A-deficient mice. Our study suggests that the bHLH protein tal-1 contributes to leukemia by interfering with E2A protein function(s).

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

Similar content being viewed by others

References

  • Abraham KM, Levin SD, Marth JD, Forbush KA, Perlmutter RM . 1991 Proc. Natl. Acad. Sci. USA 88: 3977–3981

  • Anderson KP, Crable SC, Lingrel JB . 1998 J. Biol. Chem. 273: 14347–14354

  • Bain G, Engel I, Robanus-Maandag EC, teRiele HPJ, Voland JR, Sharp L, Chun J, Huey B, Pinkel D, Murre C . 1997 Mol. Cell. Biol. 17: 4782–4791

  • Bash RO, Hall S, Timmons CF, Crist WM, Amylon M, Smith RG, Baer R . 1995 Blood 86: 666–676

  • Begley CG, Green AR . 1999 Blood 93: 2760–2770

  • Brennan TJ, Chakraborty T, Olson EN . 1991 Proc. Natl. Acad. Sci. USA 88: 5675–5679

  • Cohen-Kaminsky S, Maouche-Chretien L, Vitelli L, Vinit MA, Blanchard L, Yamamoto M, Peshcle C, Romeo PH . 1998 EMBO J. 17: 5151–5160

  • Condorelli G, Vitelli L, Valtieri M, Marta I, Montesoro E, Lulli V, Baer R, Peschle C . 1995 Blood 86: 164–175

  • Condorelli GL, Facchiano F, Valtieri M, Proietti E, Vitelli L, Lulli V, Huebner K, Peschle C, Croce CM . 1996 Cancer Res. 56: 5113–5119

  • Davis RL, Cheng PF, Lassar AB, Weintraub H . 1990 Cell 60: 733–746

  • Doyle K, Zhang Y, Baer R, Bina M . 1994 J. Biol. Chem. 269: 12099–12105

  • Early P, Rogers J, Davis M, Calame K, Bond M, Wall R, Hood L . 1980 Cell 20: 313–319

  • Grimm S, Bauer MKA, Baeuerle PA, Schulze-Osthoff K . 1988 J. Cell. Biol. 134: 13–23

  • Henthorn P, Kiledjian M, Kadesch T . 1990 Science 247: 467–470

  • Hsu H, Huang L, Tsan JT, Funk W, Wright WE, Hu JS, Kingston B, Baer R . 1994a Mol. Cell. Biol. 14: 1256–1265

  • Hsu H, Wadman I, Baer R . 1994b Proc. Natl. Acad. Sci. USA 91: 3181–3185

  • Hsu HL, Wadman I, Tsan JT, Baer R . 1994c Proc. Natl. Acad. Sci. USA 91: 5947–5951

  • Hsu HL, Cheng JT, Chen Q, Baer R . 1991 Mol. Cell. Biol. 11: 3037–3042

  • Hu JS, Olson EN, Kingston RE . 1992 Mol. Cell. Biol. 12: 1031–1042

  • Huang S, Qui Y, Stein RW, Brandt SJ . 1999 Oncogene 18: 4958–4967

  • Huang S, Qui Y, Shi Y, Xu Z, Brandt SJ . 2000 EMBO J. 19: 6792–6803

  • Huang S, Brandt SJ . 2000 Mol. Cell. Biol. 20: 2248–2259

  • Johnson SE, Wang X, Hardy S, Taparowsky EJ, Konieczny SF . 1996 Mol. Cell. Biol. 16: 1604–1613

  • Kelliher MA, Seldin D, Leder P . 1996 EMBO J. 15: 5160–5166

  • Krieg PA, Melton DA . 1987 Methods Enzymol. 155: 397–415

  • Lassar AB, Davis RL, Wright WE, Kadesch T, Murre C, Voronova A, Baltimore D, Weintraub H . 1991 Cell 66: 305–315

  • Larson RC, Lavenir I, Larson TA, Baer R, Warren AJ, Wadman I, Nottage K, Rabbitts TH . 1996 EMBO J. 15: 1021–1027

  • Littlewood T, Evan GI . 1998 Helix-Loop-Helix Transcription Factors Oxford: University Press

  • Malissen M, Minard K, Mjolsness S, Kronenberg M, Goverman J, Hunkapiller T, Prystowsky MB, Yoshikai Y, Fitch F, Mak TW . 1984 Cell 37: 1101–1110

  • Murre C, McCaw PS, Baltimore D . 1989 Cell 56: 777–783

  • Park ST, Sun XH . 1998 J. Biol. Chem. 273: 7030–7037

  • Porcher C, Swat W, Rockwell K, Fujiwara Y, Alt F, Orkin SH . 1996 Cell 86: 47–57

  • Porcher CL, EC, Fujiwara Y, Zon LI, Orkin SH . 1999 Development 126: 4603–4615

  • Prabhu S, Ignatova A, Park ST, Sun XH . 1997 Mol. Cell. Biol. 17: 5888–5896

  • Sawada S, Littman DR . 1993 Mol. Cell. Biol. 13: 5620–5628

  • Seldin DC, Leder P . 1995 Science 267: 894–897

  • Shivdasani RA, Mayer EL, Orkin SH . 1995 Nature 373: 432–434

  • Taketo M, Schroeder AC, Mobraaten LE, Gunning KB, Hanten G, Fox RR, Roderick TH, Stewart CL, Lilly F, Hansen CT, Overbeek PA . 1991 Proc. Natl. Acad. Sci. USA 88: 2065–2069

  • Valge-Archer VE, Osada H, Warren AJ, Forster A, Li J, Baer R, Rabbitts TH . 1994 Proc. Natl. Acad. Sci. USA 91: 8617–8621

  • Visvader JE, Mao X, Fujiwara Y, Hahm K, Orkin SH . 1997 Proc. Natl. Acad. Sci. USA 94: 13707–13712

  • Visvader JE, Fujiwara Y, Orkin SH . 1998 Genes Dev. 12: 473–479

  • Voronova AF, Lee F . 1994 Proc. Natl. Acad. Sci. USA 91: 5952–5956

  • Vyas P, McDevitt MA, Cantor AB, Katz S, Fujiwara Y, Orkin SH . 1999 Development 126: 2799–2811

  • Wadman I, Li J, Bash RO, Forster A, Rabbitts TH, Baer R . 1994 EMBO J. 13: 4831–4839

  • Wadman IS, Osada H, Grutz GG, Agulnick AD, Westphal H, Forster A, Rabbitts TH . 1997 EMBO J. 16: 3145–3157

  • Warren AJ, Colledge WH, Carlton MBL, Evans MJ, Smith AJH, Rabbitts TH . 1994 Cell 78: 45–57

  • Zhuang Y, Cheng P, Weintraub H . 1996 Mol. Cell. Biol. 16: 2898–2905

Download references

Acknowledgements

The authors would like to acknowledge the expert technical assistance of the University of Massachusetts Medical School Transgenic Mouse Core Facility. M Kelliher is a recipient of a Sidney Kimmel Cancer Scholar Award.

Author information

Authors and Affiliations

  1. Department of Molecular Genetics and Microbiology and the Cancer Center, University of Massachusetts Medical School, 373 Plantation Street, Worcester, 01605, Massachusetts, MA, USA

    Jennifer O'Neil, Marilisa Billa, Sarah Oikemus & Michelle Kelliher

Authors
  1. Jennifer O'Neil
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marilisa Billa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sarah Oikemus
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michelle Kelliher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michelle Kelliher.

Rights and permissions

Reprints and permissions

About this article

Cite this article

O'Neil, J., Billa, M., Oikemus, S. et al. The DNA binding activity of TAL-1 is not required to induce leukemia/lymphoma in mice. Oncogene 20, 3897–3905 (2001). https://doi.org/10.1038/sj.onc.1204519

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204519

Keywords

This article is cited by

Search

Advanced search

Quick links