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PMID: 8700869 Published · ppublish English Journal Article

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 5 ·1996-03-05 ·Pages 1972-6

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

Abstract

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.

MeSH Terms
Apoptosis Caspase 3 Caspase 7 Caspases Cysteine Endopeptidases/metabolism Enzyme Activation Granzymes Humans Poly(ADP-ribose) Polymerases/metabolism Protein Processing, Post-Translational Proteins/metabolism Serine Endopeptidases/metabolism
Chemicals
Proteins Poly(ADP-ribose) Polymerases GZMB protein, human Granzymes Serine Endopeptidases CASP3 protein, human CASP7 protein, human Caspase 3 Caspase 7 Caspases Cysteine Endopeptidases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Quan L T
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Tewari M
O'Rourke K
Dixit V
Snipas S J
Poirier G G
Ray C
Pickup D J
Salvesen G S
References (44)
44 references, click to expand
  1. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  2. Interleukin-1 beta converting enzyme: a novel cysteine protease required for IL-1 beta production and implicated in programmed cell death.
    Protein Sci. 1995 Jan;4(1):3-12 PMID: 7773174
  3. Pericellular proteolysis by neutrophils in the presence of proteinase inhibitors: effects of substrate opsonization.
    J Cell Biol. 1988 Mar;106(3):667-76 PMID: 3279049
  4. Structural and functional analysis of poly(ADP ribose) polymerase: an immunological study.
    Biochim Biophys Acta. 1988 Jul 13;950(2):147-60 PMID: 2454668
  5. Cytotoxic T lymphocyte mediated cytolysis.
    Biochemistry. 1988 Apr 19;27(8):2641-6 PMID: 3042021
  6. The effect of poly(ADP-ribosyl)ation on native and H1-depleted chromatin. A role of poly(ADP-ribosyl)ation on core nucleosome structure.
    J Biol Chem. 1989 May 25;264(15):8878-86 PMID: 2498319
  7. Product review. New mammalian expression vectors.
    Nature. 1990 Nov 1;348(6296):91-2 PMID: 2234068
  8. Human and murine cytotoxic T lymphocyte serine proteases: subsite mapping with peptide thioester substrates and inhibition of enzyme activity and cytolysis by isocoumarins.
    Biochemistry. 1991 Feb 26;30(8):2217-27 PMID: 1998680
  9. Molecular cloning of the interleukin-1 beta converting enzyme.
    Science. 1992 Apr 3;256(5053):97-100 PMID: 1373520
  10. A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes.
    Nature. 1992 Apr 30;356(6372):768-74 PMID: 1574116
  11. Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme.
    Cell. 1992 May 15;69(4):597-604 PMID: 1339309
  12. Purification of three cytotoxic lymphocyte granule serine proteases that induce apoptosis through distinct substrate and target cell interactions.
    J Exp Med. 1992 Dec 1;176(6):1521-9 PMID: 1460416
  13. The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme.
    Cell. 1993 Nov 19;75(4):641-52 PMID: 8242740
  14. Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3.
    Cell. 1993 Nov 19;75(4):653-60 PMID: 8242741
  15. Rapid purification of cationic granule proteases: application to human granzymes.
    Protein Expr Purif. 1993 Oct;4(5):398-404 PMID: 8251751
  16. Prevention of vertebrate neuronal death by the crmA gene.
    Science. 1994 Feb 11;263(5148):826-8 PMID: 8303301
  17. Premature p34cdc2 activation required for apoptosis.
    Science. 1994 Feb 25;263(5150):1143-5 PMID: 8108732
  18. Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase.
    Cell. 1995 Jun 2;81(5):801-9 PMID: 7774019
  19. Identification and characterization of ICH-2, a novel member of the interleukin-1 beta-converting enzyme family of cysteine proteases.
    J Biol Chem. 1995 Jun 23;270(25):15250-6 PMID: 7797510
  20. Molecular cloning and pro-apoptotic activity of ICErelII and ICErelIII, members of the ICE/CED-3 family of cysteine proteases.
    J Biol Chem. 1995 Jun 30;270(26):15870-6 PMID: 7797592
  21. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis.
    Nature. 1995 Jul 6;376(6535):37-43 PMID: 7596430
  22. Purification of an interleukin-1 beta converting enzyme-related cysteine protease that cleaves sterol regulatory element-binding proteins between the leucine zipper and transmembrane domains.
    J Biol Chem. 1995 Jul 28;270(30):18044-50 PMID: 7629113
  23. Cleavage of poly(ADP-ribose) polymerase by interleukin-1 beta converting enzyme and its homologs TX and Nedd-2.
    J Biol Chem. 1995 Aug 11;270(32):18715-8 PMID: 7642516
  24. CrmA-inhibitable cleavage of the 70-kDa protein component of the U1 small nuclear ribonucleoprotein during Fas- and tumor necrosis factor-induced apoptosis.
    J Biol Chem. 1995 Aug 11;270(32):18738-41 PMID: 7543896
  25. Cytotoxic lymphocytes require granzyme B for the rapid induction of DNA fragmentation and apoptosis in allogeneic target cells.
    Cell. 1994 Mar 25;76(6):977-87 PMID: 8137431
  26. Inhibition of interleukin-1 beta converting enzyme by the cowpox virus serpin CrmA. An example of cross-class inhibition.
    J Biol Chem. 1994 Jul 29;269(30):19331-7 PMID: 8034697
  27. Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death.
    Cell. 1994 Sep 9;78(5):739-50 PMID: 8087842
  28. Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE.
    Nature. 1994 Sep 22;371(6495):346-7 PMID: 8090205
  29. Apoptotic cell death induced by intracellular proteolysis.
    J Immunol. 1994 Nov 1;153(9):4247-55 PMID: 7930626
  30. Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1 beta-converting enzyme.
    Genes Dev. 1994 Jul 15;8(14):1613-26 PMID: 7958843
  31. Specific cleavage of the 70-kDa protein component of the U1 small nuclear ribonucleoprotein is a characteristic biochemical feature of apoptotic cell death.
    J Biol Chem. 1994 Dec 9;269(49):30757-60 PMID: 7983001
  32. CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme.
    J Biol Chem. 1994 Dec 9;269(49):30761-4 PMID: 7983002
  33. Fas- and tumor necrosis factor-induced apoptosis is inhibited by the poxvirus crmA gene product.
    J Biol Chem. 1995 Feb 17;270(7):3255-60 PMID: 7531702
  34. Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock.
    Cell. 1995 Feb 10;80(3):401-11 PMID: 7859282
  35. The Fas death factor.
    Science. 1995 Mar 10;267(5203):1449-56 PMID: 7533326
  36. Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme.
    Science. 1995 Mar 31;267(5206):2000-3 PMID: 7535475
  37. Expression, refolding, and autocatalytic proteolytic processing of the interleukin-1 beta-converting enzyme precursor.
    J Biol Chem. 1995 Apr 21;270(16):9378-83 PMID: 7721861
  38. Involvement of an ICE-like protease in Fas-mediated apoptosis.
    Nature. 1995 May 4;375(6526):78-81 PMID: 7536900
  39. Requirement of an ICE/CED-3 protease for Fas/APO-1-mediated apoptosis.
    Nature. 1995 May 4;375(6526):81-3 PMID: 7536901
  40. Granzyme B is inhibited by the cowpox virus serpin cytokine response modifier A.
    J Biol Chem. 1995 May 5;270(18):10377-9 PMID: 7737968
  41. A novel human protease similar to the interleukin-1 beta converting enzyme induces apoptosis in transfected cells.
    EMBO J. 1995 May 1;14(9):1914-22 PMID: 7743998
  42. Interleukin-1 beta converting enzyme requires oligomerization for activity of processed forms in vivo.
    EMBO J. 1995 May 1;14(9):1923-31 PMID: 7743999
  43. What do dysfunctional serpins tell us about molecular mobility and disease?
    Nat Struct Biol. 1995 Feb;2(2):96-113 PMID: 7749926
  44. Human plasma proteinase inhibitors.
    Annu Rev Biochem. 1983;52:655-709 PMID: 6193754
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.5.1972
Published
1996-03-05
Pages
1972-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC39893
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.93.5.1972 PMC Full Text View journal details
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