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:

Interaction with GATA transcription factors provides a mechanism for cell-specific effects of c-Fos

Oncogene volume 22, pages 8403–8412 (2003)Cite this article

Abstract

c-Fos is a multifunctional transcription factor that is involved in cellular proliferation, differentiation and apoptosis. c-Fos is rapidly induced by a variety of hormones, growth factors and other extracellular stimuli, resulting in cell-specific responses. One potential mechanism underlying the cell-specific effects of c-Fos may be its ability to regulate gene expression through interaction with tissue-restricted transcription factors. We report here that c-Fos interacts with the cell-specific GATA proteins to potentiate their ability to transactivate target promoters, via GATA-binding sites. c-Fos is recruited to GATA proteins through direct interaction with their N-terminal activation domain. Neither the leucine zipper nor the DNA-binding domain of c-Fos is required for physical interaction with GATA proteins. Instead, a C-terminal domain located between amino acids 235 and 296, which is conserved in FosB but not in the nontransforming Fos family members, FosB/SF or Fra-1, is essential for c-Fos-GATA interaction. These data suggest that c-Fos may act as an inducible cofactor for cell-specific transcription factors and unravel a novel mechanism for transcriptional regulation by c-Fos, independent of the well-studied AP-1 pathway. The results also raise the possibility that dysregulated interaction with cell-specific transcription factors may be an important component in cellular transformation by nuclear oncogenes.

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

  • Angel P, Hattori K, Smeal T and Karin M . (1988). Cell, 55, 875–885.

  • Bannister AJ and Kouzarides T . (1995). EMBO J., 14, 4758–4762.

  • Bhalla SS, Robitaille L and Nemer M . (2001). J. Biol. Chem., 276, 11439–11445.

  • Bockamp EO, Fordham JL, Gottgens B, Murrell AM, Sanchez MJ and Green AR . (1998). J. Biol. Chem., 273, 29032–29042.

  • Cantor AB and Orkin SH . (2002). Oncogene, 21, 3368–3376.

  • Charron F, Paradis P, Bronchain O, Nemer G and Nemer M . (1999). Mol. Cell. Biol., 19, 4355–4365.

  • Charron F, Tsimiklis G, Arcand M, Robitaille L, Liang Q, Molkentin JD, Meloche S and Nemer M . (2001). Genes Dev., 15, 2702–2719.

  • Chen L, Glover JN, Hogan PG, Rao A and Harrison SC . (1998). Nature, 392, 42–48.

  • Ciapponi L, Jackson DB, Mlodzik M and Bohmann D . (2001). Genes Dev., 15, 1540–1553.

  • Deng T and Karin M . (1994). Nature, 371, 171–175.

  • Depre C, Shipley GL, Chen W, Han Q, Doenst T, Moore ML, Stepkowski S, Davies PJ and Taegtmeyer H . (1998). Nat. Med., 4, 1269–1275.

  • Durocher D, Charron F, Warren R, Schwartz RJ and Nemer M . (1997). EMBO J., 16, 5687–5696.

  • Fantz DA, Jacobs D, Glossip D and Kornfeld K . (2001). J. Biol. Chem., 276, 27256–27265.

  • Fox AH, Kowalski K, King GF, Mackay JP and Crossley M . (1998). J. Biol. Chem., 273, 33595–33603.

  • Gottgens B, Barton LM, Chapman MA, Sinclair AM, Knudsen B, Grafham D, Gilbert JGR, Rogers J, Bentley DR and Green AR . (2002). Genome Res., 12, 749–759.

  • Grépin C, Dagnino L, Robitaille L, Haberstroh L, Antakly T and Nemer M . (1994). Mol. Cell. Biol., 14, 3115–3129.

  • Grigoriadis AE, Wang ZQ, Cecchini MG, Hofstetter W, Felix R, Fleisch HA and Wagner EF . (1994). Science, 266, 443–448.

  • Herzig TC, Jobe SM, Aoki H, Molkentin JD, Cowley Jr AW, Izumo S and Markham BE . (1997). Proc. Natl. Acad. Sci. USA, 94, 7543–7548.

  • Hosoda K, Hammer RE, Richardson JA, Baynash AG, Cheung JC, Giaid A and Yanagisawa M . (1994). Cell, 79, 1267–1276.

  • Hu E, Mueller E, Oliviero S, Papaioannou VE, Johnson R and Spiegelman BM . (1994). EMBO J., 13, 3094–3103.

  • Jacobs D, Glossip D, Xing HM, Muslin AJ and Kornfeld K . (1999). Genes Dev., 13, 163–175.

  • Jochum W, Passegue E and Wagner EF . (2001). Oncogene, 20, 2401–2412.

  • Johnson RS, Spiegelman BM and Papaioannou VE . (1992). Cell, 71, 577–586.

  • Karin M and Chang L . (2001). J. Endocrinol., 169, 447–451.

  • Kataoka K, Noda M and Nishizawa M . (1996). Oncogene, 12, 53–62.

  • Kawana M, Lee ME, Quertermous EE and Quertermous T . (1995). Mol. Cell. Biol., 15, 4225–4231 3.

  • Kuo CT and Leiden JM . (1999). Annu. Rev. Immunol., 17, 149–187.

  • Lassar AB, Thayer MJ, Overell RW and Weintraub H . (1989). Cell, 58, 659–667.

  • Li L, Chambard JC, Karin M and Olson EN . (1992). Genes Dev., 6, 676–689.

  • Liang Q, De Windt LJ, Witt SA, Kimball TR, Markham BE and Molkentin JD . (2001). J. Biol. Chem., 276, 30245–30253.

  • Lim KC, Lakshmanan G, Crawford SE, Gu Y, Grosveld F and Engel JD . (2000). Nat. Genet., 25, 209–212.

  • Lord KA, Abdollahi A, Hoffman-Liebermann B and Liebermann DA . (1993). Mol. Cell. Biol., 13, 841–851.

  • Lowry JA and Atchley WR . (2000). J. Mol. Evol., 50, 103–115.

  • Macian F, Garcia-Rodriguez C and Rao A . (2000). EMBO J., 19, 4783–4795.

  • Matsuo K, Owens JM, Tonko M, Elliott C, Chambers TJ and Wagner EF . (2000). Nat. Genet., 24, 184–187.

  • McBride K and Nemer M . (1998). Mol. Cell. Biol., 18, 5073–5081.

  • McBride K and Nemer M . (2001). Can. J. Physiol. Pharmacol., 79, 673–681.

  • Miyamoto T, Ohneda O, Arai F, Iwamoto K, Okada S, Takagi K, Anderson DM and Suda T . (2001). Blood, 98, 2544–2554.

  • Morin S, Charron F, Robitaille L and Nemer M . (2000). EMBO J., 19, 2046–2055.

  • Morin S, Paradis P, Aries A and Nemer M . (2001). Mol. Cell. Biol., 21, 1036–1044.

  • Nemer G and Nemer M . (2003). Dev. Biol., 254, 131–148.

  • Nemer G, Qureshi SA, Malo D and Nemer M . (1999). Mamm. Genome, 10, 993–999.

  • Ofir R, Dwarki VJ, Rashid D and Verma IM . (1990). Nature, 348, 80–82.

  • Pandey KL, Pavlou SN, Kovacs WJ and Inagami T . (1986). Biochem. Biophys. Res. Commun., 138, 399–404.

  • Saez E, Rutberg SE, Mueller E, Oppenheim H, Smoluk J, Yuspa SH and Spiegelman BM . (1995). Cell, 82, 721–732.

  • Schreiber M, Baumann B, Cotten M, Angel P and Wagner EF . (1995). EMBO J., 14, 5338–5349.

  • Schultheiss TM, Burch JB and Lassar AB . (1997). Genes Dev., 11, 451–462.

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

  • Shivdasani RA, Fujiwara Y, McDevitt MA and Orkin SH . (1997). EMBO J., 16, 3965–3973.

  • Stein B, Baldwin Jr AS, Ballard DW, Greene WC, Angel P and Herrlich P . (1993). EMBO J., 12, 3879–3891.

  • Sutherland JA, Cook A, Bannister AJ and Kouzarides T . (1992). Genes Dev., 6, 1810–1819.

  • Takayanagi H, Kim S, Matsuo K, Suzuki H, Suzuki T, Sato K, Yokochi T, Oda H, Nakamura K, Ida N, Wagner EF and Taniguchi T . (2002). Nature, 416, 744–749.

  • Tsai FY, Keller G, Kuo FC, Weiss M, Chen J, Rosenblatt M, Alt FW and Orkin SH . (1994). Nature, 371, 221–226.

  • Wang ZQ, Ovitt C, Grigoriadis AE, Mohle-Steinlein U, Ruther U and Wagner EF . (1992). Nature, 360, 741–745.

  • Wenzel A, Iseli HP, Fleischmann A, Hafezi F, Grimm C, Wagner EF and Reme CE . (2002). J. Neurochem., 80, 1089–1094.

  • Wisdom R, Yen J, Rashid D and Verma IM . (1992). Genes Dev., 6, 667–675.

  • Yamagata T, Nishida J, Sakai R, Tanaka T, Honda H, Hirano N, Mano H, Yazaki Y and Hirai H . (1995). Mol. Cell. Biol., 15, 3830–3839.

  • Zheng W and Flavell RA . (1997). Cell, 89, 587–596.

Download references

Acknowledgements

We are grateful to Lynda Robitaille for valuable technical assistance and to Lise Laroche for expert secretarial help. We thank Dr Pierre Paradis for editorial assistance. This work was supported by a grant from the Cancer Research Society Inc. and, in part, by the Canadian Institutes of Health Research (MOP-36382). FC was the recipient of a studentship from the National Cancer Institute of Canada. MN holds a Canada Research Chair in Molecular Biology.

Author information

Author notes

  1. Kevin McBride

    Present address: Compatigene, Biotechnology Research Institute, 6100 Royalmount, Montréal, QC, Canada, H4P 2R2

Authors and Affiliations

  1. Laboratoire de Développement et différenciation cardiaques, Institut de recherches cliniques de Montréal (IRCM), 110, avenue des Pins Ouest, Montréal, H2W 1R7, QC, Canada

    Kevin McBride, Frédéric Charron, Chantal Lefebvre & Mona Nemer

  2. Department of Medicine, McGill University, Montréal, QC, Canada

    Kevin McBride, Frédéric Charron, Chantal Lefebvre & Mona Nemer

Authors
  1. Kevin McBride
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frédéric Charron
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chantal Lefebvre
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mona Nemer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mona Nemer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McBride, K., Charron, F., Lefebvre, C. et al. Interaction with GATA transcription factors provides a mechanism for cell-specific effects of c-Fos. Oncogene 22, 8403–8412 (2003). https://doi.org/10.1038/sj.onc.1206877

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206877

Keywords

This article is cited by

Search

Advanced search

Quick links