Advertisement

Recruitment of enzymes and stress proteins as lens crystallins

  • Joram Piatigorsky
  • Marc Kantorow
  • Rashmi Gopal-Srivastava
  • Stanislav I. Tomarev
Part of the Experientia book series (EXS, volume 71)

Summary

The major water-soluble proteins — or crystallins — of the eye lens are either identical to or derived from proteins with non-refractive functions in numerous tissues. In general, the recruitment of crystallins has come from metabolic enzymes (usually with detoxification functions) or stress proteins. Some crystallins have been recruited without duplication of the original gene (i.e., lactate dehydrogenase B and α-enolase), while others have incurred one (i.e., argininosuccinate lyase and a small heat shock protein) or several (i.e., glutathione S-transferase) gene duplications. Enzyme (or stress protein)-crystallins often maintain their non-refractive function in the lens and/or other tissues as well as their refractive role, a process we call gene sharing. α-Crystallin/small heat shock protein/molecular chaperone is of special interest since it is the major crystallin of humans. There are two α-crystallin genes (αA and αB), with αB retaining the full functions of a small heat shock protein. Here we describe recent evidence indicating that αA and αB have kinase activity, which would make them members of the enzyme-crystallins. We also describe various regulatory elements of the mouse α-crystallin genes responsible for their expression in the lens and, for αB, in skeletal muscle. Delineating the control elements for gene expression of these multifunctional protective proteins provides the foundations for their eventual use in gene therapy. Finally, comparison of the mouse and chicken αAcrystallin genes reveals similarities and differences in their functional cis-acting elements, indicative of evolution at the level of gene regulation.

Keywords

Gene Duplication Stress Protein Aldehyde Dehydrogenase Small Heat Shock Protein Lens Crystallins 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bhat, S.P. and Nagineni, C.N. (1989) αB subunit of lens-specific α-crystallin in other ocular and non-ocular tissues. Biochem. Biophys. Res. Comm. 158: 319–325.Google Scholar
  2. Cuthbertson, R.A., Tomarev, S.I. and Piatigorsky, J. (1992) Taxon-specific recruitment of enzymes as major soluble proteins in the corneal epithelium of three mammals, chicken, and squid. Proc. Natl. Acad. Sci. USA 89: 4004–4008.PubMedCrossRefGoogle Scholar
  3. Dasgupta, S., Hohman, T.C. and Carper, D. (1992) Hypertonic stress induces aB-crystallin expression. Exp. Eye Res. 54: 461–470.PubMedCrossRefGoogle Scholar
  4. Jong, W.W., Hendriks, W., Mulders, J.W.M. and Bloemendal, H. (1989) Evolution of eye lens crystallins: the stress connection. TIBS 14: 365–368.PubMedGoogle Scholar
  5. Jong, W.W., Leunissen, J.A.M., and Voorter, C.E.M. (1993) Evolution of the acrystallin/small heat shock protein family. Mol. Cell. Biol. 10: 103–126.Google Scholar
  6. Dubin, R.A., Gopal-Srivastava, R., Wawrousek, E.F. and Piatigorsky, J. (1991) Expression of the murine aB-crystallin gene in lens and skeletal muscle: identification of a muscle-preferred enhancer. Mol. Cell. Biol. 11: 4340–4349.PubMedGoogle Scholar
  7. Dubin, R.A., Wawrousek, E.F. and Piatigorsky, J. (1989) Expression of the murine aBcrystallin gene is not restricted to the lens. Mol. Cell. Biol. 9: 1083–1091.PubMedGoogle Scholar
  8. Gopal-Srivastava, R. and Piatigorsky, J. (1993) The murine aB-crystallin/small heat shock protein enhancer: identification of aBE-1, aBE-2, aBE-3, and MRF control elements. Mol. Cell. Biol. 13: 7144–7152.PubMedGoogle Scholar
  9. Horwitz, J. (1992) A-crystallin can function as a molecular chaperone. Proc. Natl. Acad. Sci. USA 89: 10449–10453.PubMedCrossRefGoogle Scholar
  10. Iwaki, T., Iwaki, A., Miyazono, M. and Goldman, J.E. (1991) Preferential expression of a crystallin in astrocytic elements of neuroectodermal tumors. Cancer 68: 2230–2240.PubMedCrossRefGoogle Scholar
  11. Iwaki, T. and Tateishi, J. (1991) Immunohistochemical demonstration of alphaB-crystallin in harmatomas of tuberous sclerosis. Am. J. Path. 139: 1303–1308.PubMedGoogle Scholar
  12. Jaworski, C.J., Chepelinsky, A.B. and Piatigorsky, J. (1991) The aA-crystallin gene: conserved features of the 5’ flanking regions in human, mouse, and chicken. J. Mol. Biol. 33: 495–505.Google Scholar
  13. Kantorow, M., Becker, K., Sax, C.M., Ozato, K. and Piatigorsky, J. (1993) Binding of tissue-specific forms of aA-CRYBP1 to its regulatory sequence in the mouse aA-crystallin gene: double-label immunoblotting of UV-crosslinked complexes. Gene 131: 159–165.PubMedCrossRefGoogle Scholar
  14. Kato, K., Shinohara, H., Kurobe, N., Goto, S., Inaguma, Y. and Ohshima, K. (1991) Immunoreactive aA-crystallin in rat non-lenticular tissues detected with a sensitive immunoassay method. Biochim. Biophys. Acta 1080: 173–180.Google Scholar
  15. Klement, J.F., Wawrousek, E.F. and Piatigorsky, J. (1989) Tissue-specific expression of the chicken aA-crystallin gene in cultured lens epithelia and transgenic mice. J. Biol. Chem. 264: 19837–19844.Google Scholar
  16. Klement, J.F., Cvekl, A. and Piatigorsky, J. (1993) Functional elements DE2A, DE2B, and DE1A and the TATA box are required for activity of the chicken aA-crystallin gene in transfected lens epithelial cells. J. Biol. Chem. 268: 6777–6784.Google Scholar
  17. Klemenz, R., Frohli, E., Aoyama, A., Hoffmann, S., Simpson, R.J., Moritz, R.L., and Schafer, R. (1991a) aB-crystallin accumulation is a specific response to Ha-ras and v-mos oncogene expression in mouse NIH 3T3 fibroblasts. Mol. Cell. Biol. 11: 803–812.Google Scholar
  18. Klemenz, R., Frohli, E., Steiger, R.H., Schafer, R. and Aoyama, A. (1991b) aB-crystallin is a small heat shock protein. Proc. Natl. Acad. Sci. USA 88: 3652–3656.Google Scholar
  19. Lee, D.C., Kim, R.Y. and Wistow, G.J. (1993) An avian aB-crystallin: non-lens expression and sequence similarities with both small (HSP27) and large (HSP70) heat shock proteins. J. Mol. Biol. 232: 1221–1226.Google Scholar
  20. Matsuo, I. and Yasuda, K. (1992) The cooperative interaction between two motifs of an enhancer element of the chicken aA-crystallin gene, aCE1 and aCE2, confers lens-specific expression. Nucl. Acids Res. 20: 3701–3712.Google Scholar
  21. Nakamura, T., Donovan, D.M., Hamada, K., Sax, C.M., Norman, B., Flanagan, J.R., Ozato, K., Westphal, H. and Piatigorsky, J. (1990) Regulation of the mouse aA-crystallin gene: isolation of a cDNA encoding a protein that binds to a cis sequence motif shared with the major histocompatibility complex class I gene and other genes. Mol. Cell. Biol. 10: 3700–3708.Google Scholar
  22. Piatigorsky, J. (1992) Lens crystallins. Innovation associated with changes in gene regulation. J. Biol. Chem. 267: 4277–4280.Google Scholar
  23. Piatigorsky, J. and Wistow, G.J. (1989) Enzyme/crystallins: gene sharing as an evolutionary strategy. Cell 57: 197–199.PubMedCrossRefGoogle Scholar
  24. Piatigorsky, J. and Wistow, G.J. (1991) The recruitment of crystallins: new functions precede gene duplication. Science 252: 1078–1079.CrossRefGoogle Scholar
  25. Sax, C.M., Ilagan, J.G. and Piatigorsky, J. (1993) Functional reduncancy of the DE-1 and aACRYBP1 regulatory sites of the mouse aA-crystallin promoter. Nucl. Acids Res. 21: 26332640.Google Scholar
  26. Sax, C.M., Klement, J.F. and Piatigorsky, J. (1990) Species-specific lens activation of the thymidine kinase promoter by a single copy of the mouse aA-CRYBP1 site and loss of tissue specificity by multimerization. Mol. Cell. Biol. 10: 6813–6816.Google Scholar
  27. Srinivasan, A.N., Nagineni, C.N. and Bhat, S.P. (1992) AA-crystallin is expressed in nonocular tissues. J. Biol. Chem. 267: 23337–23341.Google Scholar
  28. Sax, C.M. and Piatigorsky, J. (1993) Expression of the a-crystallin/small heat shock protein/molecular chaperone genes in the lens and other tissues. Adv. Enzymol., in press.Google Scholar
  29. Spector, A., Chiesa, R., Sredy, J. and Garner, W. (1985) CAMP-dependent phosphorylation of bovine lens a-crystallin. Proc. Natl. Acad. Sci. USA 82: 4712–4716.PubMedCrossRefGoogle Scholar
  30. Tomarev, S.I., Zinovieva, R.D., Guo, K. and Piatigorsky, J. (1993) Squid glutathione Stransferase. Relationships with other glutathione S-transferases and S-crystallins of cephalopods. J. Biol. Chem. 268: 4534–4542.PubMedGoogle Scholar
  31. Tomarev, S.I., Zinovieva, R.D. and Piatigorsky, J. (1991) Crystallins of the octopus lens. Recruitment from detoxification enzymes. J. Biol. Chem. 266: 24226–24231.PubMedGoogle Scholar
  32. Tomarev, S.I., Zinovieva, R.D. and Piatigorsky, J. (1992) Characterization of squid crystallin genes. Comparison with mammalian glutathione S-transferase genes. J. Biol. Chem. 267: 8604–8612.PubMedGoogle Scholar
  33. Voorter, C.E.M., Mulders, J.W.M., Bloemendal, H. and de Jong, W.W. (1986) Some aspects of the phosphorylation of a-crystallin A. Eur. J. Biochem. 160: 203–210.CrossRefGoogle Scholar
  34. Wistow, G. (1993) Lens crystallins: gene recruitment and evolutionary dynamism. TIBS 18: 301–306.PubMedGoogle Scholar
  35. Wistow, G.J. and Kim, H. (1991) Lens protein expression in mammals: taxon-specificity and the recruitment of crystallins. J. Mol. Evol. 32: 262–269.PubMedCrossRefGoogle Scholar
  36. Wistow, G.J. and Piatigorsky, J. (1987) Recruitment of enzymes as lens structural proteins. Science 236: 1554–1556.PubMedCrossRefGoogle Scholar
  37. Wistow, G.J. and Piatigorsky, J. (1988) Lens crystallins: The evolution and expression of proteins for a highly specialized tissue. Annu. Rev. Biochem. 57: 479–504.PubMedCrossRefGoogle Scholar
  38. Zinovieva, R.D., Tomarev, S.I. and Piatigorsky, J. (1993) Aldehyde dehydrogenase-derived Ucrystallins of squid and octopus. Specialization for lens expression. J. Biol. Chem. 268: 11449–11455.PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 1994

Authors and Affiliations

  • Joram Piatigorsky
    • 1
  • Marc Kantorow
    • 1
  • Rashmi Gopal-Srivastava
    • 1
  • Stanislav I. Tomarev
    • 1
  1. 1.Laboratory of Molecular and Developmental Biology, National Eye InstituteNational Institutes of HealthBethesdaUSA

Personalised recommendations