The retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity (original) (raw)

Nature volume 329, pages 642–645 (1987)Cite this article

Abstract

The human gene (RB) that determines susceptibility to hereditary retinoblastoma has been identified recently by molecular genetic techniques1,2,14. Previous results indicate that complete inactiva-tion of the RB gene is required for tumour formation. As a 'cancer suppressor' gene, RB thus functions in a manner opposite to that of most other oncogenes. Sequence analysis of RB complementary DNA clones demonstrated a long open reading frame encoding a hypothetical protein with features suggestive of a DNA-binding function2. To further substantiate and identify the RB protein, we have prepared rabbit antisera against a trypE-RB fusion protein. The purified anti-RB IgG immunoprecipitates a protein doublet with apparent relative molecular mass (_M_r) of 110,000–114,000. The specific protein(s) are present in all cell lines expressing normal RB mRNA, but are not detected in five retinoblastoma cell lines examined. The RB protein can be metabolically labelled with 32P-phosphoric acid, indicating that it is a phosphoprotein. Biochemical fractionation and immunofluorescence studies demonstrate that the majority of the protein is located within the nucleus. Furthermore, the protein can be retained by and eluted from DNA-cellulose columns, suggesting that it is associated with DNA binding activity. Taken together, these results imply that the RB gene product may function in regulating other genes within the cell.

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References

  1. Friend, S. et al. Nature 323, 643–645 (1986).
    Article ADS CAS Google Scholar
  2. Lee, W. H. et al. Science 235, 1394–1399 (1987).
    Article ADS CAS Google Scholar
  3. Spindler, K., Rosser, D. & Berk, J. Virology 49, 132–141 (1984).
    CAS Google Scholar
  4. Boyle, W. J., Lipsick, J. S. & Baluda, M. A. Proc. natn. Acad. Sci. U.S.A. 83, 4685–4689 (1986).
    Article ADS CAS Google Scholar
  5. Lee, W. H., Wheatley, W., Benedict, W., Huang, C. M. & Lee, E. Y. H. P. Proc. natn Acad. Sci. U.S.A. 83, 6790–6794 (1986).
    Article ADS CAS Google Scholar
  6. Seeger, R. C. et al. New Engl. J. Med. 313, 1111–1116 (1985).
    Article CAS Google Scholar
  7. McFall, R. C., Sery, T. W. & Makedon, M. Cancer Res. 37, 1003–1010 (1977).
    CAS PubMed Google Scholar
  8. Tai, T. et al. J. biol. Chem. 250, 8569–8575 (1975).
    CAS PubMed Google Scholar
  9. Comings, D. E. Proc. natn. Acad. Sci. U.S.A. 70, 3324–3328 (1973).
    Article ADS CAS Google Scholar
  10. Lee, W. H., Murphree, A. L. & Benedict, B. W. Nature 309, 458–460 (1984).
    Article ADS CAS Google Scholar
  11. Radke, K. et al. J. Cell Biol. 97, 1601–1611 (1983).
    Article CAS Google Scholar
  12. Ramsay, G., Stanton, L., Schwab, M. & Bishop, J. M. Molec. Cell Biol. 6, 4450–4457 (1986).
    Article CAS Google Scholar
  13. Weiss, R., Teich, N., Varmus, H. & Coffin, J. RNA Tumor Viruses (Cold Spring Harbor Laboratory, New York, (1985).
    Google Scholar
  14. Fung, Y. K. T. et al. Science 236, 1657–1661 (1987).
    Article ADS CAS Google Scholar

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Author notes

  1. Theodore W. Sery and Larry A. Donoso: Wills Eye Hospital, Ninth and Walnut Street, Philadelphia, Pennsylvania 19107, USA

Authors and Affiliations

  1. Experimental Pathology Program and Center for Molecular Genetics, Department of Pathology M-012, University of California San Diego, School of Medicine, La Jolla, California, 92093, USA
    Wen-Hwa Lee, Jin-Yuh Shew, Frank D. Hong, Theodore W. Sery, Larry A. Donoso, Lih-Jiuan Young, Robert Bookstein & Eva Y.-H. P. Lee

Authors

  1. Wen-Hwa Lee
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  2. Jin-Yuh Shew
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  3. Frank D. Hong
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  4. Theodore W. Sery
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  5. Larry A. Donoso
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  6. Lih-Jiuan Young
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  7. Robert Bookstein
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  8. Eva Y.-H. P. Lee
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Lee, WH., Shew, JY., Hong, F. et al. The retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity.Nature 329, 642–645 (1987). https://doi.org/10.1038/329642a0

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