Transformation by ras modifies AP1 composition and activity (original) (raw)

Oncogene volume 14, pages 837–847 (1997)Cite this article

Abstract

The Ras proteins play a central role in regulating cell growth and their mutation can lead to abnormal proliferation. To analyse the potential link betwen AP1 activity, encoded by members of the jun and fos gene families, and Ras-mediated cellular transformation, we have studied several NIH3T3 clones which overexpress the Ha-Ras or Ki-Ras oncogenes. These transformed fibroblasts accumulated higher levels of cJun, JunB, Fra1 and Fra2 proteins relative to their normal counterparts. They also displayed increased AP1 DNA binding activity which was predominantly composed of cJun and Fra1 containing dimers. Following serum stimulation of Ras clones, the elevated levels of cJun and Fra1 remained steady, while the induction of JunB and Fra2 was partially attenuated. Moreover, deregulated Ras signaling resulted in a complete loss of the serum inducibility of cFos and FosB. Ectopic co-expression of cJun and Fra1 in NIH3T3 fibroblasts led to a transformed phenotype, attenuation of cFos serum inducibility, increased AP1 activity and Cyclin D1 accumulation, all characteristics of oncogenic Ras expressing cells. These results demonstrate that cJun and Fra1 are crucial mediators of the Ras-transformation process.

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Authors and Affiliations

  1. Unité des Virus Oncogènes; URA 1644 du CNRS, Département des Biotechnologies, Institut Pasteur, 25, rue du Dr Roux
    Dominique Lallemand & Moshe Yaniv
  2. URA 1644 du CNRS, Département des Biotechnologies, Institut Pasteur, 25, rue du Dr Roux, Paris, Cedex 15 75724, France
    Dominique Lallemand & Moshe Yaniv
  3. Unité INSERM 368, Biologie Moléculaire du Développement, ENS, 46 rue d'Ulm., Paris, Cedex 05 75230, France
    Fatima Mechta
  4. Department of Cell Biology and Biochemistry, Texas Tech University Health Science Center, 3601 4th Street, Lubbock, 79430, Texas, USA
    Curt M Pfarr

Authors

  1. Fatima Mechta
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  2. Dominique Lallemand
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  3. Curt M Pfarr
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  4. Moshe Yaniv
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Mechta, F., Lallemand, D., Pfarr, C. et al. Transformation by ras modifies AP1 composition and activity.Oncogene 14, 837–847 (1997). https://doi.org/10.1038/sj.onc.1200900

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