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AP-1 dimers regulate transcription of the p14/p19ARF tumor suppressor gene

Oncogene volumeĀ 24,Ā pages 2298ā€“2306 (2005)Cite this article

Abstract

Evidence is accumulating about the role of individual AP-1 components in cell proliferation and transformation. Notably, Ras-mediated transformation is characterized by the upregulation of particular AP-1 members, such as c-Jun and Fra-1. The p14/p19ARF tumor suppressor gene is a key link between oncogenic Ras signaling and the p53 pathway. We explored the involvement of AP-1 dimers in the transcriptional regulation of the p14/p19ARF gene. We demonstrate that both the human and mouse ARF promoters are transcriptional targets of selective AP-1 dimers. The ARF promoter is regulated specifically by AP-1 heterodimers containing Fra-1. Overexpression of c-Junāˆ¼Fra-1 dimers in primary murine fibroblast cells led to the upregulation of the endogenous ARF protein and growth arrest. Conversely, inhibition of c-Jun or Fra-1 protein levels resulted in decreased ARF expression. In addition, we show that AP-1 dimers cooperate with oncogenic Ras in the transcriptional activation of the p14/p19ARF promoter. Thus, AP-1 heterodimers may contribute to the regulation of ARF expression upon oncogenic signaling.

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Acknowledgements

We are grateful to P Jones, C Sherr, D Ginsberg and G Langsley for providing reagents. We thank M Pontoglio, S Ait-Si-Ali and L Casalino for helpful discussions and advice. This work was supported by grants from the EC Biomed and Training and Mobility Programs, the Pasteur-Weizmann Foundation and the Association for International Cancer Research (AICR). MAZ was supported by the Ligue contre le Cancer, the Pasteur Institute and AICR. MW was supported by La Fondation pour la Recherche MĆ©dicale (FRM). LB was supported by an EMBO fellowship.

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  1. Unit of Gene Expression and Disease, Department of Developmental Biology, Pasteur Institute, 25, rue du Docteur Roux, 75724, Paris Cedex, 15, France

    Maya Ameyar-Zazoua,Ā Marta B Wisniewska,Ā Moshe YanivĀ &Ā Jonathan B Weitzman

  2. Research Institute of Molecular Pathology, Dr Bohr-Gasse 7, Vienna, A-1030, Austria

    Latifa BakiriĀ &Ā Erwin F Wagner

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  1. Maya Ameyar-Zazoua
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Correspondence to Jonathan B Weitzman.

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Ameyar-Zazoua, M., Wisniewska, M., Bakiri, L. et al. AP-1 dimers regulate transcription of the p14/p19ARF tumor suppressor gene. Oncogene 24, 2298ā€“2306 (2005). https://doi.org/10.1038/sj.onc.1208424

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