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Alpha1-antitrypsin: Structure, function and molecular biology of the gene

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Bioscience Reports

Abstract

Alpha1-antitrypsin (AAT) deficiency is one of the commonest inherited disorders in white Caucasians. This association has provided major insights into the pathogenesis of chronic lung disease. The three dimensional structure of the protein and the structure of the gene have been determined. Some of the signals required for regulation of expression and tissue-specificity have been defined. Genetic manipulation of active site residues may provide a new generation of biological compounds with potential therapeutic applications.

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References

  1. Carrell, R. W., Jeppsson, J.-O., Laurell, C.-B., Brennan, S. O., Owen, M. C., Vaughan, L. and Boswell, D. R. (1983)Nature (Lond.)298:329.

    Google Scholar 

  2. Laurell, C.-B. and Eriksson, S. (1963)Scand. J. Lab. Invest. 15:132.

    Google Scholar 

  3. Kilburn, K. H. and McKenzie, W. (1975)Science 189:634.

    Google Scholar 

  4. Carp, H., Miller, F. and Hoidal, J. R. (1982)Proc. Natl. Acad. Sci. USA 79:2041.

    Google Scholar 

  5. Carrell, R. W., Jeppsson, J.-O., Vaughan, L., Brennan, S., Owen, M. and Boswell, D. R. (1981)FEBS Lett. 135:301.

    Google Scholar 

  6. Loebermann, H., Tokuoka, R., Deisenhofer, J. and Huber, R. (1987)J. Mol. Biol. 177:531.

    Google Scholar 

  7. Johnson, D. A. and Travis, J. (1976)Biochem. Biophys. Res. Commun. 72:33.

    Google Scholar 

  8. Carrell, R. W. and Owen, M. C. (1985)Nature (Lond.)317:730.

    Google Scholar 

  9. Takemura, S., Rossing, T. H. and Perlmutter, D. H. (1986)J. Clin. Invest. 77:1207.

    Google Scholar 

  10. Banda, M. J., Rice, A. G., Griffin, G. L. and Senior R. M. (1988)J. Exp. Med. 167:1608.

    Google Scholar 

  11. Beatty, K., Bieth, J. and Travis, J. (1980)J. Biol. Chem. 255: 3931.

    Google Scholar 

  12. Carrell, R. W. (1986)J. Clin. Invest. 78:1427.

    Google Scholar 

  13. Owen, M. C., Brennan, S. O., Lewis, J. H. and Carrell, R. W. (1983)N. Engl. J. Med. 309:694.

    Google Scholar 

  14. Courtney, M., Jallat, S., Tessier, L. H., Benavente, A., Crystal, R. G. and Le Cocq, J. P. (1985)Nature (Lond.)313:149.

    Google Scholar 

  15. Jallat, S., Carvallo, D., Tessier, L. H., Roecklin, D., Roitsch, C., Ogushi, F., Crystal, R. G. and Courtney M. (1986)Prot. Engin. 1:29.

    Google Scholar 

  16. Mornex, J.-F., Chytil-Weir, A., Martinet, Y., Courteney, M., Le Cocq, J.-P. and Crystal, R. G. (1986)J. Clin. Invest. 77:1952.

    Google Scholar 

  17. Kelsey, G. D., Povey, S., Bygrave, A. E. and Lovell-Badge, R. H. (1987)Genes and Development 1:161.

    Google Scholar 

  18. Carlson, J. A., Rogers, B. B., Sifers, R. N., Hawkins, H. L., Finegold, M. J. and Woo, S. L. C. (1988)J. Clin. Invest. 82:26.

    Google Scholar 

  19. Hercz, A. (1985)Biochem. Biophys. Res. Commun. 128:199.

    Google Scholar 

  20. Nukiwa, T., Brantly, M., Ogushi, F., Fells, G. A., Satoh, K., Stier, L., Courtney, M. and Crystal, R. G. (1987)Biochemistry 26:5259.

    Google Scholar 

  21. Brantly, M., Nukiwa, T., Ogushi, F., Fells, G. A., Stier, L. and Crystal, R. G. (1988)Am. Rev. Resp. Med. 137:A210.

    Google Scholar 

  22. Jeppsson, J.-O. and Laurell, C.-B. (1988)FEBS Lett. 231:327.

    Google Scholar 

  23. Owen, H. M. C. and Carrell, R. W. (1976)Br. Med. J. i:130.

    Google Scholar 

  24. Yoshida, A., Lieberman, J., Gaidulis, I. and Ewing, C. (1976).Proc. Natn. Acad. Sci. USA 73:1324.

    Google Scholar 

  25. Hofker, M. H., Nukiwa, T., van Paassen H. M. B., Nelen, M., Frants, R. R., Klasen, E. C. and Crystal, R. G. (1987)Am. J. Hum. Genet. 41:A220.

    Google Scholar 

  26. Takahashi, H., Nukiwa, T., Ogushi, F., Brantly, M., Courtney, M. and Crystal, R. G. (1987)Am. Rev. Resp. Dis. 135:A66.

    Google Scholar 

  27. Satoh, K., Nukiwa, T., Brantly, M., Garver, R. I., Hofker, M., Courtney, M. and Crystal, R. G. (1988)Am. J. Hum. Genet. 42:77.

    Google Scholar 

  28. Nukiwa, T., Takahashi, H., Brantly, M. Courtney, M. and Crystal, R. G. (1987)J. Biol. Chem. 262:11999.

    Google Scholar 

  29. Curiel, D., Brantly, M., Curiel, E., Stier, L. and Crystal, R. (1988)Am. Rev. Resp. Dis. 137:A210.

    Google Scholar 

  30. Hardick, C., Sifers, R., Carlson, J., Kidd, V. and Woo, S. L. C. (1986)AM. J. Hum. Genet. 39:A202.

    Google Scholar 

  31. Foreman, R. C. (1987)FEBS Lett. 216:79.

    Google Scholar 

  32. Schindler, D. (1984) In:Advances in Gene Technology, (Ahmad, S. A., Black, S., Schulz, J., Scott, W. and Whelan, J., Eds), Cambridge University Press, Cambridge, UK, pp. 32.

    Google Scholar 

  33. Cox, D. W., Woo, S. L. C. and Mansfield, T. (1985)Nature (Lond.)316:79.

    Google Scholar 

  34. Hodgson, I. and Kalsheker N. (1987)J. Med. Gen.,24:47.

    Google Scholar 

  35. Kalsheker, N. A., Hodgson, I. J., Watkins, G. L., White, J. P., Morrison, H. M. and Stockley, R. A. (1987)Brit. Med. J. 294:1511.

    Google Scholar 

  36. Buraczynska, M., Schott, D., Hanzh, K. A., Holtmann, B. and Ulmer, W. (1987)Klin Wochenschr. 65:538.

    Google Scholar 

  37. Goedde, H. W., Hirth, L., Bankmann, H. G., Pellicer, A., Pellicer, T., Stahn, M. and Singh, S. (1973)Hum. Hered. 23:135.

    Google Scholar 

  38. Fagerhol, M. K. and Gedde-Dahl, Jr. T. (1969)Hum. Hered. 19:3.

    Google Scholar 

  39. Kueppers, F. (1972) In:Pulmonary Emphysema and Proteolysis (Mittman, C., Ed.), Academic Press, New York, pp. 133.

    Google Scholar 

  40. Chakraborty, R., Constans, J. and Majumder, P. P. (1982)Hum. Genet. 62:193.

    Google Scholar 

  41. Lai, E. C., Kao, F.-T., Law, M. L. and Woo, S. L. C. (1983)Am. J. Hum. Genet. 35:385.

    Google Scholar 

  42. Long, G. L., Chandra, T., Woo, S. L. C., Davie, E. W. and Kurachi, K. (1984)Biochemistry 23:4828.

    Google Scholar 

  43. Leicht, M., Long, G. L., Chandra, T., Kurachi, K., Mace, M., Jr., Davie, E. W. and Woo, S. L. C. (1982)Nature (Lond.)297:655.

    Google Scholar 

  44. Ciliberto, G., Dente, L. and Cortese, R. (1985)Cell 41:531.

    Google Scholar 

  45. Perlino, E., Cortese, R. and Ciliberto, G. (1987)EMBO J. 6:2767.

    Google Scholar 

  46. Green, S., Walter, P., Kumar, V., Krust, A., Bornet, J. M., Argos, P. and Chambon, P. (1986)Nature (Lond.)320:134.

    Google Scholar 

  47. Krust, A., Green, S., Argos, P., Vijay, K., Walter, P., Bornet, J. M. and Chambon, P. (1986)EMBO J. 5:891.

    Google Scholar 

  48. Schneider, C. and Williams, J. G. (1985)J. Cell Sci. Suppl. 3:139.

    Google Scholar 

  49. Mueller, P. P. and Hinnebush, A. G. (1986)Cell 45:201.

    Google Scholar 

  50. Hardon, E. M., Frain, M., Paonessa, G. and Cortese R. (1988)EMBO J. 7: 1711.

    Google Scholar 

  51. Grayson, D. R., Costa, R. H., Xanthopoulos, K. G. and Darnell, J. E. (1988)Science 239:786.

    Google Scholar 

  52. Costa, R. H., Grayson, D. R., Kleanthis, G. X. and Darnell, J. E. (1988)Proc. Natl. Acad. Sci. USA 85:3840.

    Google Scholar 

  53. Dickson, I. and Alper, C. A. (1974)Clin. Chim. Acta 54:381.

    Google Scholar 

  54. Gauldie, J., Richards, C., Harnish, D., Lansdorp, P. M. and Baumann, H. (1987)Proc. Natl. Acad. Sci. USA 84:7251.

    Google Scholar 

  55. Perlmutter, D. H., Dinarello, C. I., Punsal, P. I. and Colten, H. R. (1986)J. Clin. Invest. 787:1349.

    Google Scholar 

  56. Swanson, T., Kalsheker, N., Neale, M. L. and Matthews, N.Biochem. Soc. Trans. (in press).

  57. Perlmutter, D. H., Travis, J. and Punsal, P. I. (1988)J. Clin. Invest. 81:1774.

    Google Scholar 

  58. Tanaka, T., Ohkubo, H. and Nakanishi, S. (1984)J. Biol. Chem. 259:8063.

    Google Scholar 

  59. Reed, L., Bao, J. J., Sifers, R. and Woo, S. L. C. (1987)Am. J. Hum. Genet. 41:A235.

    Google Scholar 

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  1. Department of Medical Biochemistry, University of Wales College of Medicine, Royal Infirmary, Newport Road, CF2 1SZ, Cardiff

    N. Kalsheker

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Kalsheker, N. Alpha1-antitrypsin: Structure, function and molecular biology of the gene. Biosci Rep 9, 129–138 (1989). https://doi.org/10.1007/BF01115992

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