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TOJ3, a target of the v-Jun transcription factor, encodes a protein with transforming activity related to human microspherule protein 1 (MCRS1)

Oncogene volume 20, pages 7524–7535 (2001)Cite this article

Abstract

Using the established quail cell line Q/d3 conditionally transformed by the v-jun oncogene, cDNA clones (TOJ2, TOJ3, TOJ5, TOJ6) were isolated by representational difference analysis (RDA) that correspond to genes which were induced immediately upon conditional activation of v-jun. One of these genes, TOJ3, is immediately and specifically activated after doxycycline-mediated v-jun induction, with kinetics similar to the induction of well characterized direct AP-1 target genes. TOJ3 is neither activated upon conditional activation of v-myc, nor in cells or cell lines non-conditionally transformed by oncogenes other than v-jun. Sequence analysis revealed that the TOJ3-specific cDNA encodes a 530-amino acid protein with significant sequence similarities to the murine or human microspherule protein 1 (MCRS1, MSP58), a nucleolar protein that directly interacts with the ICP22 regulatory protein from herpes simplex virus 1 or with p120, a proliferation-related protein expressed at high levels in most human malignant tumor cells. Similar to its mammalian counterparts, the TOJ3 protein contains a bipartite nuclear localization motif and a forkhead associated domain (FHA). Using polyclonal antibodies directed against a recombinant amino-terminal TOJ3 protein segment, the activation of TOJ3 in jun-transformed fibroblasts was also demonstrated at the protein level by specific detection of a polypeptide with an apparent Mr of 65 000. Retroviral expression of the TOJ3 gene in quail or chicken embryo fibroblasts induces anchorage-independent growth, indicating that the immediate activation of TOJ3 in fibroblasts transformed by the v-jun oncogene contributes to cell transformation.

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Acknowledgements

We are grateful to Bernard Roizman (The University of Chicago, USA) for the p78 specific antiserum and to Friedrich Lottspeich (Max-Planck-Institute of Biochemistry, Martinsried, Germany) for mass spectrometry. K Bister thanks Peter K Vogt for support during a sabbatical stay at the Scripps Research Institute, La Jolla, CA, USA. We thank Doris Bratschun and Martina Texler for excellent technical assistance. This work was supported by grants SFB-F002/211 from the Austrian Science Foundation (FWF) and 7357 from the Austrian National Bank.

Accession numbers

The sequences reported in this paper have been deposited in the GenBank database, www.ncbi.nlm.nih.gov (accession nos. AY007310, AF390033, AF390034, AF390035).

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  1. Institute of Biochemistry, University of Innsbruck, Peter-Mayr-Str. 1a, Innsbruck, A-6020, Austria

    Andreas G Bader, Martin L Schneider, Klaus Bister & Markus Hartl

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  1. Andreas G Bader
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Correspondence to Markus Hartl.

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Bader, A., Schneider, M., Bister, K. et al. TOJ3, a target of the v-Jun transcription factor, encodes a protein with transforming activity related to human microspherule protein 1 (MCRS1). Oncogene 20, 7524–7535 (2001). https://doi.org/10.1038/sj.onc.1204938

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