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.
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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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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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DOI: https://doi.org/10.1038/sj.onc.1204938
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