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.

  • Short Report
  • Published:

Elevated c-Jun expression in acute myeloid leukemias inhibits C/EBPα DNA binding via leucine zipper domain interaction

Oncogene volume 22, pages 4760–4764 (2003)Cite this article

Abstract

Transcription factor C/EBPα induces normal myeloid differentiation, inactivation of C/EBPα leads to a differentiation block in acute myeloid leukemias (AML), and overexpression of C/EBPα results in AML growth arrest and differentiation. Recent reports suggest that C/EBPα is activated or inactivated via protein–protein interactions. We previously reported that C/EBPα needs to inactivate the proto-oncogene c-Jun via leucine zipper domain interaction in order to induce granulocytic differentiation. We, therefore, hypothesized that c-Jun expression might be elevated in AML and subsequently inactivate C/EBPα. In fact, compared to normal bone marrow mononuclear cells, c-Jun expression is increased in AML patient samples (Affymetrix expression microarray analysis, n=166). c-Jun binds to C/EBPα via the leucine zipper domains and prevents C/EBPα from DNA binding. Inactivation of C/EBPα by c-Jun is necessary for c-Jun to induce proliferation because c-Jun-induced proliferation can be prevented by ectopic overexpression of C/EBPα. The dominant-negative 30-kDa C/EBPα protein, found in AML, fails to downregulate c-Jun mRNA expression in AML patient samples. Thus, our data suggest a model for AML in which c-Jun promotes proliferation and prevents differentiation by inhibiting C/EBPα DNA binding via leucine zipper domain interaction. It might depend on the expression levels of C/EBPα and c-Jun, if inhibition of C/EBPα by c-Jun or if inhibition of c-Jun by C/EBPα is more predominant: proliferation versus differentiation; AML versus normal myeloid development.

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

Similar content being viewed by others

References

  • Behre G, Singh SM, Liu H, Bortolin LT, Christopeit M, Radomska HS, Rangatia J, Hiddemann W, Friedman AD and Tenen DG . (2002). J. Biol. Chem., 277, 26293–26299.

  • Behre G, Whitmarsh AJ, Coghlan MP, Hoang T, Carpenter CL, Zhang DE, Davis RJ and Tenen DG . (1999). J. Biol. Chem., 274, 4939–4946.

  • Burgess GS, Williamson EA, Cripe LD, Litz-Jackson S, Bhatt JA, Stanley K, Stewart MJ, Kraft AS, Nakshatri H and Boswell HS . (1998). Blood, 92, 2450–2460.

  • Elsaesser A, Franzen M, Kohlmann A, Weisser M, Schnittger S, Update.Schoch C, Reddy V, Burel S, Zhang DE, Ueffing M, Tenen DG, Hiddemann W and Behre G . (2003). Oncogene, in press.

  • Gombart AF, Hofmann WK, Kawano S, Takeuchi S, Krug U, Kwok SH, Larsen RJ, Asou H, Miller CW, Hoelzer D and Koeffler HP . (2002). Blood, 99, 1332–1340.

  • Iwama A, Osawa M, Hirasawa R, Uchiyama N, Kaneko S, Onodera M, Shibuya K, Shibuya A, Vinson C, Tenen DG and Nakauchi H . (2002). J. Exp. Med., 195, 547–558.

  • McKnight SL . (2001). Cell, 107, 259–261.

  • Miller M, Shuman JD, Sebastian T, Dauter Z and Johnson PF . (2003). J. Biol. Chem., 2003 Feb 10 [epub ahead of print].

  • Mizuki M, Schwaeble J, Steur C, Choudhary C, Agrawal S, Sargin B, Steffen B, Matsumura I, Kanakura Y, Boehmer FD, Mueller-Tidow C, Berdel WE and Serve H . (2002). Blood 2002 Dec 5 [epub ahead of print].

  • Mueller BU, Pabst T, Osato M, Asou N, Johansen LM, Minden MD, Behre G, Hiddemann W, Ito Y and Tenen DG . (2002). Blood, 100, 998–1007.

  • Pabst T, Mueller BU, Harakawa N, Schoch C, Haferlach T, Behre G, Hiddemann W, Zhang DE and Tenen DG . (2001a). Nat. Med., 7, 444–451.

  • Pabst T, Mueller BU, Zhang P, Radomska HS, Narravula S, Schnittger S, Behre G, Hiddemann W and Tenen DG . (2001b). Nat. Genet., 27, 263–270.

  • Peer Zada AA, Singh SM, Meisel A, Reddy VA, Elsaesser A, Update.Haferlach T, Tenen DG, Hiddemann W and Behre G . (2003). Oncogene, 22, 2296–2308.

  • Perrotti D, Cesi V, Trotta R, Guerzoni C, Santilli G, Campbell K, Iervolino A, Condorelli F, Gambacorti-Passerini C, Caligiuri MA and Calabretta B . (2002). Nat. Genet., 30, 48–58.

  • Porse BT, Pedersen TA, Xu X, Lindberg B, Wewer UM, Friis-Hansen L and Nerlov C . (2001). Cell, 107, 247–258.

  • Preudhomme C, Sagot C, Boissel N, Cayuela JM, Tigaud I, de Botton S, Thomas X, Raffoux E, Lamandin C, Castaigne S, Fenaux P and Dombret H . (2002). Blood, 100, 2717–2723.

  • Radomska HS, Huettner CS, Zhang P, Cheng T, Scadden DT and Tenen DG . (1998). Mol. Cell. Biol., 18, 4301–4314.

  • Rangatia J, Vangala RK, Treiber N, Zhang P, Radomska H, Tenen DG, Hiddemann W and Behre G . (2002). Mol. Cell. Biol., 22, 8681–8694.

  • Reddy VA, Iwama A, Iotzova G, Schulz M, Elsasser A, Vangala RK, Tenen DG, Hiddemann W and Behre G . (2002). Blood, 100, 483–490.

  • Schoch C, Kohlmann A, Schnittger S, Brors B, Dugas M, Mergenthaler S, Kern W, Hiddemann W, Eils R and Haferlach T . (2002). Proc. Natl. Acad. Sci. USA, 99, 10008–10013.

  • Schuster C, Forster K, Dierks H, Elsaesser A, Behre G, Simon N, Danhauser-Riedl S, Hallek M and Warmuth M . (2003). Blood, 101, 655–663.

  • Schwartz C, Beck K, Mink S, Schmolke M, Budde B, Wenning D and Klempnauer KH . (2003). EMBO J., 22, 882–892.

  • Shaulian E and Karin M . (2002). Nat. Cell Biol., 4, E131–E136.

  • Tenen DG . (2003). Nat. Rev. Cancer, 3, 89–101.

  • Truong BT, Lee YJ, Lodie TA, Park DJ, Perrotti D, Watanabe N, Koeffler HP, Nakajima H, Tenen DG and Kogan SC . (2003). Blood, 101, 1141–1148.

  • Vangala RK, Heiss-Neumann MS, Rangatia JS, Singh SM, Schoch C, Tenen DG, Hiddemann W and Behre G . (2003). Blood, 101, 270–277.

  • Waalwijk Van Doorn-Khosravani SB, Erpelinck C, Meijer J, Van Oosterhoud S, Van Putten WL, Valk PJ, Beverloo HB, Tenen DG, Lowenberg B and Delwel R . (2002). Hematol. J., 3, 324.

  • Wang H, Goode T, Iakova P, Albrecht JH and Timchenko NA . (2002). EMBO J., 21, 930–941.

  • Wang H, Iakova P, Wilde M, Welm A, Goode T, Roesler WJ and Timchenko NA . (2001). Mol. Cell, 8, 817–828.

  • Zhang DE, Zhang P, Wang ND, Hetherington CJ, Darlington GJ and Tenen DG . (1997). Proc. Natl. Acad. Sci. USA, 94, 569–574.

  • Zhang P, Behre G, Pan J, Iwama A, Wara-Aswapati N, Radomska HS, Auron PE, Tenen DG and Sun Z . (1999). Proc. Natl. Acad. Sci. USA, 96, 8705–8710.

Download references

Author information

Authors and Affiliations

  1. Medicine III at University of Munich Hospital Grosshadern and GSF Research Center, Munich, Germany

    Janki Rangatia, Rajani K Vangala, Sheo M Singh, Abdul A Peer Zada, Annika Elsässer, Alexander Kohlmann, Torsten Haferlach, Wolfgang Hiddemann & Gerhard Behre

  2. Harvard Institutes of Medicine, Harvard Medical School, Boston, MA, USA

    Daniel G Tenen

Authors
  1. Janki Rangatia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rajani K Vangala
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sheo M Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Abdul A Peer Zada
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Annika Elsässer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alexander Kohlmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Torsten Haferlach
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Daniel G Tenen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wolfgang Hiddemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Gerhard Behre
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gerhard Behre.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rangatia, J., Vangala, R., Singh, S. et al. Elevated c-Jun expression in acute myeloid leukemias inhibits C/EBPα DNA binding via leucine zipper domain interaction. Oncogene 22, 4760–4764 (2003). https://doi.org/10.1038/sj.onc.1206664

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206664

Keywords

This article is cited by

Search

Advanced search

Quick links