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Partial oncogenic transformation of chicken embryo fibroblasts by Jun dimerization protein 2, a negative regulator of TRE- and CRE-dependent transcription

Oncogene volume 22, pages 2151–2159 (2003)Cite this article

Abstract

Jun dimerization protein 2 (JDP2) was identified as a bZIP protein that forms dimers with Jun proteins. JDP2 represses transcriptional activation of reporter constructs containing 12-O-tetradecanoylphorbol 13-acetate (TPA)-responsive elements (TRE) or cyclic AMP responsive elements (CRE). JDP2, overexpressed by the avian retroviral vector RCAS, induces partial oncogenic transformation of chicken embryo fibroblasts. JDP2-expressing cells form multilayered foci in monolayer cultures but do not show anchorage-independent growth. Both the carboxyl and the amino terminus of JDP2 are required for the transforming activity. Chimeric constructs of JDP2 carrying the leucine zipper domain of Fos, GCN4 or EB1 fail to transform CEF. The leucine zipper of Fos mediates only heterodimerization; it cannot homodimerize. In contrast, the leucine zippers of GCN4 and of EB1 exclusively homodimerize and do not form dimers with other bZip proteins. The results with the JDP2 chimeras suggest that the JDP2 homodimer and the JDP2/Jun heterodimer (or other bZip heterodimers formed with the Fos leucine zipper) are nontransforming, leaving as possible transforming combination the JDP2/Fos heterodimer. The unexpected transforming activity of a negative regulator of TRE- and CRE-dependent transcription raises an important question concerning the mechanisms of transformation by the related bZIP proteins Jun and Fos that address the same target sequences.

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Acknowledgements

This work was supported by grants from the National Cancer Institute. This is manuscript number 14291-MEM of the Department of Molecular and Experimental Medicine, The Scripps Research Institute. Lesli LeCompte and Mohamed Abu-Qaoud provided competent and dedicated technical assistance. We thank Dr George Miller for a gift of an EB1 clone, a gene of Epstein–Barr virus that codes for a Jun-related bZIP protein.

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Author notes

  1. Erik Blazek

    Present address: University of Munich, GSF R.208, Marchioninistrasse 25, 81377, Munich, Germany

  2. Ulrich Kruse

    Present address: Cellzome AG, Meyerhofstr. 1, 69117, Heidelberg, Germany

Authors and Affiliations

  1. Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, CA, USA

    Erik Blazek, Sibylle Wasmer, Ulrich Kruse, Masahiro Aoki & Peter K Vogt

  2. Technion-Israel Institute of Technology, P.O. Box 9649, Bat-Galim, Haifa, 31096, Israel

    Ami Aronheim

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Correspondence to Peter K Vogt.

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Blazek, E., Wasmer, S., Kruse, U. et al. Partial oncogenic transformation of chicken embryo fibroblasts by Jun dimerization protein 2, a negative regulator of TRE- and CRE-dependent transcription. Oncogene 22, 2151–2159 (2003). https://doi.org/10.1038/sj.onc.1206312

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