Sensitization of stefin B-deficient thymocytes towards staurosporin-induced apoptosis is independent of cysteine cathepsins

FEBS Lett. 2005 Apr 11;579(10):2149-55. doi: 10.1016/j.febslet.2005.03.002.


Stefin B (cystatin B) is an inhibitor of lysosomal cysteine cathepsins and does not inhibit cathepsin D, E (aspartic) or cathepsin G (serine) proteinases. In this study, we have investigated apoptosis triggered by camptothecin, staurosporin (STS), and anti-CD95 monoclonal antibody in the thymocytes from the stefin B-deficient mice and wild-type mice. We have observed increased sensibility to STS-induced apoptosis in the thymocytes of stefin B-deficient mice. Pretreatment of cells with pan-caspase inhibitor z-Val-Ala-Asp(OMe)-fluoromethylketone completely inhibited phosphatidylserine externalization and caspase activation, while treatment with inhibitor of calpains- and papain-like cathepsins (2S,3S)-trans-epoxysuccinyl-leucylamido-3-methyl-butane ethyl ester did not prevent caspase activation nor phosphatidylserine exposure. We conclude that sensitization to apoptosis induced by STS in thymocytes of stefin B-deficient and wild-type mice is not dependent on cathepsin inhibition by stefin B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Animals
  • Apoptosis / drug effects*
  • Cathepsins / antagonists & inhibitors
  • Cathepsins / metabolism*
  • Cells, Cultured
  • Cystatin B
  • Cystatins / metabolism*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Flow Cytometry
  • Mice
  • Mice, Inbred BALB C
  • Staurosporine / pharmacology*
  • Thymus Gland / cytology
  • Thymus Gland / drug effects*
  • Thymus Gland / enzymology
  • Thymus Gland / metabolism


  • Amino Acid Chloromethyl Ketones
  • Cstb protein, mouse
  • Cystatins
  • Cysteine Proteinase Inhibitors
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • Cystatin B
  • Cathepsins
  • Staurosporine