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Proteolytic activation of the cell death protease Yama/CPP32 by granzyme B.

Publication ,  Journal Article
Quan, LT; Tewari, M; O'Rourke, K; Dixit, V; Snipas, SJ; Poirier, GG; Ray, C; Pickup, DJ; Salvesen, GS
Published in: Proc Natl Acad Sci U S A
March 5, 1996

The serine protease granzyme B, which is secreted by cytotoxic cells, is one of the major effectors of apoptosis in susceptible targets. To examine the apoptotic mechanism of granzyme B, we have analyzed its effect on purified proteins that are thought to be components of death pathways inherent to cells. We demonstrate that granzyme B processes interleukin 1beta-converting enzyme (ICE) and the ICE-related protease Yama (also known as CPP32 or apopain) by limited proteolysis. Processing of ICE does not lead to activation. However, processing by granzyme B leads directly to the activation of Yama, which is now able to bind inhibitors and cleave the substrate poly(ADP-ribose) polymerase whose proteolysis is a marker of apoptosis initiated by several other stimuli. Thus ICE-related proteases can be activated by serine proteases that possess the correct specificity. Activation of pro-Yama by granzyme B is within the physiologic range. Thus the cytotoxic effect of granzyme B can be explained by its activation of an endogenous protease component of a programmed cell death pathway.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

March 5, 1996

Volume

93

Issue

5

Start / End Page

1972 / 1976

Location

United States

Related Subject Headings

  • Serine Endopeptidases
  • Proteins
  • Protein Processing, Post-Translational
  • Poly(ADP-ribose) Polymerases
  • Humans
  • Granzymes
  • Enzyme Activation
  • Cysteine Endopeptidases
  • Caspases
  • Caspase 7
 

Citation

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Quan, L. T., Tewari, M., O’Rourke, K., Dixit, V., Snipas, S. J., Poirier, G. G., … Salvesen, G. S. (1996). Proteolytic activation of the cell death protease Yama/CPP32 by granzyme B. Proc Natl Acad Sci U S A, 93(5), 1972–1976. https://doi.org/10.1073/pnas.93.5.1972
Quan, L. T., M. Tewari, K. O’Rourke, V. Dixit, S. J. Snipas, G. G. Poirier, C. Ray, D. J. Pickup, and G. S. Salvesen. “Proteolytic activation of the cell death protease Yama/CPP32 by granzyme B.Proc Natl Acad Sci U S A 93, no. 5 (March 5, 1996): 1972–76. https://doi.org/10.1073/pnas.93.5.1972.
Quan LT, Tewari M, O’Rourke K, Dixit V, Snipas SJ, Poirier GG, et al. Proteolytic activation of the cell death protease Yama/CPP32 by granzyme B. Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1972–6.
Quan, L. T., et al. “Proteolytic activation of the cell death protease Yama/CPP32 by granzyme B.Proc Natl Acad Sci U S A, vol. 93, no. 5, Mar. 1996, pp. 1972–76. Pubmed, doi:10.1073/pnas.93.5.1972.
Quan LT, Tewari M, O’Rourke K, Dixit V, Snipas SJ, Poirier GG, Ray C, Pickup DJ, Salvesen GS. Proteolytic activation of the cell death protease Yama/CPP32 by granzyme B. Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1972–1976.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

March 5, 1996

Volume

93

Issue

5

Start / End Page

1972 / 1976

Location

United States

Related Subject Headings

  • Serine Endopeptidases
  • Proteins
  • Protein Processing, Post-Translational
  • Poly(ADP-ribose) Polymerases
  • Humans
  • Granzymes
  • Enzyme Activation
  • Cysteine Endopeptidases
  • Caspases
  • Caspase 7