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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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.
Laurell, C.-B. and Eriksson, S. (1963)Scand. J. Lab. Invest. 15:132.
Kilburn, K. H. and McKenzie, W. (1975)Science 189:634.
Carp, H., Miller, F. and Hoidal, J. R. (1982)Proc. Natl. Acad. Sci. USA 79:2041.
Carrell, R. W., Jeppsson, J.-O., Vaughan, L., Brennan, S., Owen, M. and Boswell, D. R. (1981)FEBS Lett. 135:301.
Loebermann, H., Tokuoka, R., Deisenhofer, J. and Huber, R. (1987)J. Mol. Biol. 177:531.
Johnson, D. A. and Travis, J. (1976)Biochem. Biophys. Res. Commun. 72:33.
Carrell, R. W. and Owen, M. C. (1985)Nature (Lond.)317:730.
Takemura, S., Rossing, T. H. and Perlmutter, D. H. (1986)J. Clin. Invest. 77:1207.
Banda, M. J., Rice, A. G., Griffin, G. L. and Senior R. M. (1988)J. Exp. Med. 167:1608.
Beatty, K., Bieth, J. and Travis, J. (1980)J. Biol. Chem. 255: 3931.
Carrell, R. W. (1986)J. Clin. Invest. 78:1427.
Owen, M. C., Brennan, S. O., Lewis, J. H. and Carrell, R. W. (1983)N. Engl. J. Med. 309:694.
Courtney, M., Jallat, S., Tessier, L. H., Benavente, A., Crystal, R. G. and Le Cocq, J. P. (1985)Nature (Lond.)313:149.
Jallat, S., Carvallo, D., Tessier, L. H., Roecklin, D., Roitsch, C., Ogushi, F., Crystal, R. G. and Courtney M. (1986)Prot. Engin. 1:29.
Mornex, J.-F., Chytil-Weir, A., Martinet, Y., Courteney, M., Le Cocq, J.-P. and Crystal, R. G. (1986)J. Clin. Invest. 77:1952.
Kelsey, G. D., Povey, S., Bygrave, A. E. and Lovell-Badge, R. H. (1987)Genes and Development 1:161.
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.
Hercz, A. (1985)Biochem. Biophys. Res. Commun. 128:199.
Nukiwa, T., Brantly, M., Ogushi, F., Fells, G. A., Satoh, K., Stier, L., Courtney, M. and Crystal, R. G. (1987)Biochemistry 26:5259.
Brantly, M., Nukiwa, T., Ogushi, F., Fells, G. A., Stier, L. and Crystal, R. G. (1988)Am. Rev. Resp. Med. 137:A210.
Jeppsson, J.-O. and Laurell, C.-B. (1988)FEBS Lett. 231:327.
Owen, H. M. C. and Carrell, R. W. (1976)Br. Med. J. i:130.
Yoshida, A., Lieberman, J., Gaidulis, I. and Ewing, C. (1976).Proc. Natn. Acad. Sci. USA 73:1324.
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.
Takahashi, H., Nukiwa, T., Ogushi, F., Brantly, M., Courtney, M. and Crystal, R. G. (1987)Am. Rev. Resp. Dis. 135:A66.
Satoh, K., Nukiwa, T., Brantly, M., Garver, R. I., Hofker, M., Courtney, M. and Crystal, R. G. (1988)Am. J. Hum. Genet. 42:77.
Nukiwa, T., Takahashi, H., Brantly, M. Courtney, M. and Crystal, R. G. (1987)J. Biol. Chem. 262:11999.
Curiel, D., Brantly, M., Curiel, E., Stier, L. and Crystal, R. (1988)Am. Rev. Resp. Dis. 137:A210.
Hardick, C., Sifers, R., Carlson, J., Kidd, V. and Woo, S. L. C. (1986)AM. J. Hum. Genet. 39:A202.
Foreman, R. C. (1987)FEBS Lett. 216:79.
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.
Cox, D. W., Woo, S. L. C. and Mansfield, T. (1985)Nature (Lond.)316:79.
Hodgson, I. and Kalsheker N. (1987)J. Med. Gen.,24:47.
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.
Buraczynska, M., Schott, D., Hanzh, K. A., Holtmann, B. and Ulmer, W. (1987)Klin Wochenschr. 65:538.
Goedde, H. W., Hirth, L., Bankmann, H. G., Pellicer, A., Pellicer, T., Stahn, M. and Singh, S. (1973)Hum. Hered. 23:135.
Fagerhol, M. K. and Gedde-Dahl, Jr. T. (1969)Hum. Hered. 19:3.
Kueppers, F. (1972) In:Pulmonary Emphysema and Proteolysis (Mittman, C., Ed.), Academic Press, New York, pp. 133.
Chakraborty, R., Constans, J. and Majumder, P. P. (1982)Hum. Genet. 62:193.
Lai, E. C., Kao, F.-T., Law, M. L. and Woo, S. L. C. (1983)Am. J. Hum. Genet. 35:385.
Long, G. L., Chandra, T., Woo, S. L. C., Davie, E. W. and Kurachi, K. (1984)Biochemistry 23:4828.
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.
Ciliberto, G., Dente, L. and Cortese, R. (1985)Cell 41:531.
Perlino, E., Cortese, R. and Ciliberto, G. (1987)EMBO J. 6:2767.
Green, S., Walter, P., Kumar, V., Krust, A., Bornet, J. M., Argos, P. and Chambon, P. (1986)Nature (Lond.)320:134.
Krust, A., Green, S., Argos, P., Vijay, K., Walter, P., Bornet, J. M. and Chambon, P. (1986)EMBO J. 5:891.
Schneider, C. and Williams, J. G. (1985)J. Cell Sci. Suppl. 3:139.
Mueller, P. P. and Hinnebush, A. G. (1986)Cell 45:201.
Hardon, E. M., Frain, M., Paonessa, G. and Cortese R. (1988)EMBO J. 7: 1711.
Grayson, D. R., Costa, R. H., Xanthopoulos, K. G. and Darnell, J. E. (1988)Science 239:786.
Costa, R. H., Grayson, D. R., Kleanthis, G. X. and Darnell, J. E. (1988)Proc. Natl. Acad. Sci. USA 85:3840.
Dickson, I. and Alper, C. A. (1974)Clin. Chim. Acta 54:381.
Gauldie, J., Richards, C., Harnish, D., Lansdorp, P. M. and Baumann, H. (1987)Proc. Natl. Acad. Sci. USA 84:7251.
Perlmutter, D. H., Dinarello, C. I., Punsal, P. I. and Colten, H. R. (1986)J. Clin. Invest. 787:1349.
Swanson, T., Kalsheker, N., Neale, M. L. and Matthews, N.Biochem. Soc. Trans. (in press).
Perlmutter, D. H., Travis, J. and Punsal, P. I. (1988)J. Clin. Invest. 81:1774.
Tanaka, T., Ohkubo, H. and Nakanishi, S. (1984)J. Biol. Chem. 259:8063.
Reed, L., Bao, J. J., Sifers, R. and Woo, S. L. C. (1987)Am. J. Hum. Genet. 41:A235.
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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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DOI: https://doi.org/10.1007/BF01115992