Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma (original) (raw)

Nature volume 363, pages 640–644 (1993)Cite this article

Abstract

HUMAN myxoid liposarcomas contain a characteristic chromosomal translocation, t(12;16)(ql3;pll)1,2, that is associated with a structural rearrangement of the gene encoding CHOP 3, a growth arrest and DNA-damage inducible member of the C/EBP family of transcription factors4,5 residing on 12ql3.16. Using a CHOP-specifie complementary probe and antiserum we report here the presence of an abnormal CHOP transcript and protein in these tumours. Cloning of the translocation-associated CHOP gene product revealed a fusion between CHOP and a gene provisionally named TLS (translocated in liposarcoma). TLS is a novel nuclear RNA-binding protein with extensive sequence similarity to EWS7, the product of a gene commonly translocated in Ewing's sarcoma. In TLS-CHOP the RNA-binding domain of TLS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. Targeting of a conserved effector domain of RNA-binding proteins to DNA may play a role in tumour formation.

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References

  1. Turc-Carel, C. et al. Cancer Genet. Cytogenet. 23, 291–299 (1986).
    Article CAS Google Scholar
  2. Sreekantiaiah, S., Karakousis, C. P., Leong, S. P. L. & Sandberg, A. A. Cancer 69, 2484–2495 (1992).
    Article Google Scholar
  3. Åman, P. et al. Genes Chrom. Cancer 5, 271–277 (1992).
    Article Google Scholar
  4. Fornace, A. J. et al. Molec. cell. Biol. 9, 4196–4203 (1989).
    Article CAS Google Scholar
  5. Ron, D. & Habener, J. F. Genes Dev. 6, 439–453 (1992).
    Article CAS Google Scholar
  6. Park, J. S. et al. Gene 116, 259–267 (1992).
    Article CAS Google Scholar
  7. Delattre, O. et al. Nature 359, 162–165 (1992).
    Article ADS CAS Google Scholar
  8. Kenan, D. J., Query, C. C. & Keene, J. D. Trends biochem. Sci. 16, 214–220 (1991).
    Article CAS Google Scholar
  9. Haynes, S. R., Rebbert, M. L., Mozer, B. A., Forquignon, F. & Dawid, I. B. Proc. natn. Acad. Sci. U.S.A. 84, 1819–1823 (1987).
    Article ADS CAS Google Scholar
  10. Kiledjian, M. & Dryfuss, G. EMBO J. 11, 2655–2664 (1992).
    Article CAS Google Scholar
  11. Mitchell, P. J. & Tjian, R. Science 245, 371–378 (1989).
    Article ADS CAS Google Scholar
  12. Ghisolfi, L., Joseph, G., Amalric, F. & Erard, M. J. biol. Chem. 267, 2955–2959 (1992).
    CAS PubMed Google Scholar
  13. Cao, Z., Umek, R. M. & McKnight, S. L. Genes Dev. 5, 1538–1552 (1991).
    Article CAS Google Scholar
  14. Carlson, S. G., Fawcett, T. W., Bartlett, J. D., Bernier, M. & Holbrook, N. J. Molec. cell. Biol. (in the press).
  15. Frohman, M. A., Dush, M. K. & Martin, G. R. Proc. natn. Acad. Sci. U.S.A. 85, 8998–9002 (1988).
    Article ADS CAS Google Scholar
  16. Bugler, B. et al. J. biol. Chem. 262, 10922–10925 (1987).
    CAS PubMed Google Scholar
  17. Sachs, A. B., Bond, M. W. & Kornberg, R. D. Cell 45, 827–835 (1986).
    Article CAS Google Scholar
  18. Cretin, C. & Puigdomenech, P. Pl. molec. Biol. 15, 783–785 (1990).
    Article CAS Google Scholar

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Authors and Affiliations

  1. Departments of Medicine, Cell Biology and the Kaplan Cancer Center, NYU Medical Center, New York, New York, 10016, USA
    Anne Crozat & David Ron
  2. Department of Clinical Genetics, University Hopsital, Lund, S-22185, Sweden
    Pierre Åman & Nils Mandahl

Authors

  1. Anne Crozat
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  2. Pierre Åman
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  3. Nils Mandahl
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  4. David Ron
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Crozat, A., Åman, P., Mandahl, N. et al. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma.Nature 363, 640–644 (1993). https://doi.org/10.1038/363640a0

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