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Molecular cloning and overexpression of the human FK506-binding protein FKBP

Nature volume 346, pages 671–674 (1990)Cite this article

Abstract

THE potent immunosuppressive agent FK5061,2 is highly effective in preventing organ transplant rejection in humans3. Like cyclosporin A, FK506 inhibits the transcription of early T-cell activation genes4, apparently by modulating the activity of transcriptional regulators5 such as nuclear factor of activated T cells6. A remarkable finding is that the predominant binding proteins (immunophilins) for cyclosporin A and FK506, cyclophilin7–9 and FKBP10,11 respectively, are peptidyl-prolyl-cis–frans-isomerases that are potently and selectively inhibited by their respective ligands. Here we report the complementary DNA and derived amino-acid sequences of human FKBP from Jurkat cells and also the efficient overexpression in Escherichia coli of fully active, recombinant human FKBP. The human FKBP cDNA sequence shows significant similarity to an open reading frame in the Neisseria meningitidis genome12.

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References

  1. Thomson, A. W. Immun. Today 10, 6–9 (1989).

    Article  CAS  PubMed  Google Scholar 

  2. Tanaka, H. et al. J. Am. chem. Soc. 109, 5031–5033 (1987).

    Article  CAS  Google Scholar 

  3. Starzl, T. et al. The Lancet, ii, 1000–1004 (1989).

    Article  Google Scholar 

  4. Tocci, M. J. et al. J. Immun. 143, 718–726 (1989).

    CAS  PubMed  Google Scholar 

  5. Crabtree, G. R. Science 243, 355–361 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  6. Emmel, E. A. et al. Science 246, 1617–1620 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  7. Handschumacher, R. E., Harding, M. W., Rice, J., Drugge, R. J. & Speicher, D. W. Science 226, 544–547 (1984).

    Article  ADS  CAS  PubMed  Google Scholar 

  8. Takahashi, N., Hayano, T. & Suzuki, M. Nature 337, 473–475 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  9. Fischer, G., Wittmann-Liebold, B., Lang, K., Kiefhaber, T. & Schmid, F. X. Nature 337, 476–478 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  10. Harding, M. W., Galat, A., Uehling, D. E. & Schreiber, S. L. Nature 341, 758–760 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  11. Siekierka, J. J., Hung, S. H. Y., Poe, M., Lin, C. S. & Sigal, N. H. Nature 341, 755–757 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  12. Perry, A. C. F., Nicolson, I. J. & Saunders, J. R. J. Bact. 170, 1691–1697 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lathe, R. J. molec. Biol. 183, 1–12 (1985).

    Article  CAS  PubMed  Google Scholar 

  14. Ohara, O., Dorit, R. L. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 86, 5673–5677 (1989).

    Article  ADS  CAS  Google Scholar 

  15. Aruffo, A. & Seed, B. Proc. natn. Acad. Sci. U.S.A. 84, 8573–8577 (1987).

    Article  ADS  CAS  Google Scholar 

  16. Kozak, M. Cell 44, 283–292 (1986).

    Article  CAS  PubMed  Google Scholar 

  17. MacFerrin, K. D., Terranova, M. P., Schreiber, S. L. & Verdine, G. L. Proc. natn. Acad. Sci. U.S.A. 87, 1937–1941 (1990).

    Article  ADS  CAS  Google Scholar 

  18. Provencher, S. W. Comput. Phys. Commun. 27, 229–242 (1982).

    Article  ADS  Google Scholar 

  19. Pevsner, J., Reed, R. R. Feinstein, P. G. & Snyder, S. H. Science 241, 336–339 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  20. Hawley, D. K. & McClure, W. R. Nucleic Acids Res. 11, 2237–2255 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shine, J. & Dalgarno, L. Proc. natn. Acad. Sci. U.S.A. 71, 1342–1346 (1974).

    Article  ADS  CAS  Google Scholar 

  22. Tropschug, M., Barthelmess, I. B. & Neupert, W. Nature 342, 953–955 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  23. Dumont, F. J., Staruch, M. J., Kooprak, S. L., Melino, M. R. & Sigal, N. H. J. Immun. 144, 251–258 (1990).

    CAS  PubMed  Google Scholar 

  24. Struhl, K. Trends Biochem. Sci. 14, 137–140 (1989).

    Article  CAS  PubMed  Google Scholar 

  25. Mitchell, P. J. & Tjian, R. Science 245, 371–378 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  26. Tufty, R. M. & Kretsinger, R. H. Science 187, 167–169 (1975).

    Article  ADS  CAS  PubMed  Google Scholar 

  27. Hunt, T. Cell 59, 949–951 (1989).

    Article  CAS  PubMed  Google Scholar 

  28. Cllne, T. W. Cell 59, 231–234 (1989).

    Article  Google Scholar 

  29. Innis, M. A., Gelfand, D. H., Sninsky, J. J. & White, T. J. (eds) PCR Protocols (Academic, New York, 1990).

  30. Gyllenstein, U. B. & Erlich, H. A. Proc. natn. Acad. Sci. U.S.A. 85, 7652–7656 (1988).

    Article  ADS  Google Scholar 

  31. Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad Sci. U.S.A. 74, 5463–5467 (1977).

    Article  ADS  CAS  Google Scholar 

  32. Swain, C. G., Swain, M. S. & Berg, L. F. J. chem. Inf. Comput. Sci. 20, 47–51 (1980).

    Article  CAS  Google Scholar 

  33. Liu, J., Albers, M. W., Chen, C.-m., Schreiber, S. L. & Walsh, C. T. Proc. natn. Acad. Sci. U.S.A. 87, 2304–2308 (1990).

    Article  ADS  CAS  Google Scholar 

  34. Harrison, R. K. & Stein, R. S. Biochemistry 29, 1684–1688 (1990).

    Article  CAS  PubMed  Google Scholar 

  35. Fasman, G. D. (ed.) Practical Handbook of Biochemistry and Molecular Biology, p. 80 (CRC, Boca Raton, FL, 1989).

  36. Devereux, J., Haeberli, P. & Smithies, O. Nucleic Acids Res. 12, 387–395 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author notes

  1. Gregory L. Verdine and Stuart L. Schreiber: To whom correspondence should be addressed.

Authors and Affiliations

  1. Department of Chemistry, Harvard University, 12 Oxford Street, Cambridge, Massachusetts, 02138, USA

    Robert F. Standaert, Andrzej Galat, Gregory L. Verdine & Stuart L. Schreiber

Authors
  1. Robert F. Standaert
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  2. Andrzej Galat
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  3. Gregory L. Verdine
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  4. Stuart L. Schreiber
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Standaert, R., Galat, A., Verdine, G. et al. Molecular cloning and overexpression of the human FK506-binding protein FKBP. Nature 346, 671–674 (1990). https://doi.org/10.1038/346671a0

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