Proteolytic Activation of Human Procathepsin D

  • Gary Richo
  • Gregory E. Conner
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 306)


The occurrence of multiple proteolytic processing steps is typical of lysosomal enzyme biosynthesis, but not characteristic of the other aspartyl proteases. Cathepsin D, a lysosomal aspartyl protease, is proteolytically processed several times during biosynthesis. A summary of these processing steps is shown in Figure 1. Although the activity and structure of cathepsin D has been studied in great detail1,2,3,4 and the activation of procathepsin D is known to be dependent upon this proteolytic processing, the proteases and the exact cleavage sites which the proteases use to accomplish the processing of cathepsin D are, for the most part, unknown. The activation of the aspartyl protease proenzymes pepsinogen and prorenin has been explored in depth.4,5 In this article we have summarized our recent studies on the proteolytic activation of human procathepsin D.


Peptide Substrate Aspartic Proteinase Aspartyl Protease Human Cathepsin Miami School 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    A. J. Barrett, in: “Proteinases in Mammalian Cells and Tissues,” A. J. Barrett, ed., North Holland Publishing Co., New York, pp. 209–248 (1977).Google Scholar
  2. 2.
    G. E. Conner, G. Blobel and A. H. Erickson, in: “Lysosomes: their role in protein breakdown,” H. Glaumann and J. Ballard, eds., Academic Press, London, pp. 151–162 (1987).Google Scholar
  3. 3.
    J. G. Shewale, T. Takahashi and J. Tang, in: “Aspartic Proteinases and Their Inhibitors,” V. Kostka, ed., Walter de Gruyter, Berlin, pp. 101–116 (1985).Google Scholar
  4. 4.
    J. Tang and R. N. S. Wong, J. Cell. Biol. 33: 53–63 (1987)Google Scholar
  5. 5.
    T. Inagami, K. Misono, J.-J. Chang, Y. Takii and C. Dykes, in: “Aspartic Proteinases and Their Inhibitors,” V. Kostka, ed., Walter de Gruyter, Berlin, pp. 319–337 (1985).Google Scholar
  6. 6.
    J. Mariciniszyn, J. S. Huang, J. A. Hartsuck and J. Tang, J. Biol. Chem. 251: 7095–7102 (1976).Google Scholar
  7. 7.
    G. E. Conner, Biochem. J. 263: 601–604 (1989).PubMedGoogle Scholar
  8. 8.
    A. Hasilik, K. von Figura, E. Conzelmann, H. Nehrkorn and K. Sandhoff, Eur. J. Biochem. 125: 317–321 (1982).PubMedCrossRefGoogle Scholar
  9. 9.
    A. H. Rosenberg, B. N. Lade, D.-S. Chui, S. W. Linl, J. J. Dunn and F. W. Studier, Gene 56: 125–135 (1987).PubMedCrossRefGoogle Scholar
  10. 10.
    G. E. Conner and J. A. Udey, DNA and Cell Biology 9: 1–9 (1990).PubMedCrossRefGoogle Scholar
  11. 11.
    J. S. Huang, S. S. Huang and J. Tang, J. Biol. Chem. 254: 11405–11417 (1979).PubMedGoogle Scholar
  12. 12.
    B. M. Dunn, M. Jimenez, B. F. Parten, M. J. Valier, C. E. Rolph and J. Kay, Biochem. J. 237: 899–906 (1986).PubMedGoogle Scholar
  13. 13.
    C. W. Dykes and J. Kay, Biochem J. 153: 141–144 (1976).PubMedGoogle Scholar
  14. 14.
    K. Asbaek Christensen, V. Barkholt Pedersen and B. Foltmann, F.E.B.S. Letters 76: 214–218 (1977).CrossRefGoogle Scholar
  15. 15.
    V. Barkholt Pedersen, K. Asbaek Christensen and B. Foltmann, Eur. J. Biochem. 94: 573–580 (1979).PubMedCrossRefGoogle Scholar
  16. 16.
    T. Kageyama and K. Takahashi, in: “Aspartic Proteinases and Their Inhibitors,” V. Kostka, ed., Walter de Gruyter, Berlin, pp. 265–282 (1985).Google Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Gary Richo
    • 1
  • Gregory E. Conner
    • 1
  1. 1.Department of Cell Biology and AnatomyUniversity of Miami School of MedicineMiamiUSA

Personalised recommendations