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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Quan, LT; Tewari, M; O'Rourke, K; Dixit, V; Snipas, SJ; Poirier, GG; Ray, C; Pickup, DJ; Salvesen, GS

Published Date

  • March 1996

Published In

Volume / Issue

  • 93 / 5

Start / End Page

  • 1972 - 1976

PubMed ID

  • 8700869

Pubmed Central ID

  • 8700869

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.93.5.1972

Language

  • eng