Substrate Specificities of Caspase Family Proteases*

The caspase family represents a new class of intracellular cysteine proteases with known or suspected roles in cytokine maturation and apoptosis. These enzymes display a preference for Asp in the P1 position of substrates. To clarify differences in the biological roles of the interleukin-1β converting enzyme (ICE) family proteases, we have examined in detail the specificities beyond the P1 position of caspase-1, −2, −3, −4, −6, and −7 toward minimal length peptide substrates in vitro We find differences and similarities between the enzymes that suggest a functional subgrouping of the family different from that based on overall sequence alignment. The primary specificities of ICE homologs explain many observed enzyme preferences for macromolecular substrates and can be used to support predictions of their natural function(s). The results also suggest the design of optimal peptidic substrates and inhibitors.

[1]  Keisuke Kuida,et al.  Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice , 1996, Nature.

[2]  J. Mankovich,et al.  Preparation of an autolysis-resistant interleukin-1 beta converting enzyme mutant. , 1996, Biochemistry.

[3]  S. Srinivasula,et al.  The Ced-3/Interleukin 1β Converting Enzyme-like Homolog Mch6 and the Lamin-cleaving Enzyme Mch2α Are Substrates for the Apoptotic Mediator CPP32* , 1996, The Journal of Biological Chemistry.

[4]  Junying Yuan,et al.  Human ICE/CED-3 Protease Nomenclature , 1996, Cell.

[5]  J. Mankovich,et al.  Stability and Oligomeric Equilibria of Refolded Interleukin-1β Converting Enzyme* , 1996, The Journal of Biological Chemistry.

[6]  G. Salvesen,et al.  Molecular Ordering of Apoptotic Mammalian CED-3/ICE-like Proteases* , 1996, The Journal of Biological Chemistry.

[7]  Junying Yuan,et al.  Identification and Characterization of Ich-3, a Member of the Interleukin-1β Converting Enzyme (ICE)/Ced-3 Family and an Upstream Regulator of ICE* , 1996, The Journal of Biological Chemistry.

[8]  Y. Lazebnik,et al.  Cleavage of lamin A by Mch2 alpha but not CPP32: multiple interleukin 1 beta-converting enzyme-related proteases with distinct substrate recognition properties are active in apoptosis. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[9]  A. Zychlinsky,et al.  A bacterial invasin induces macrophage apoptosis by binding directly to ICE. , 1996, The EMBO journal.

[10]  D. Chan,et al.  Interleukin-1 beta-converting enzyme-like protease cleaves DNA- dependent protein kinase in cytotoxic T cell killing , 1996, The Journal of experimental medicine.

[11]  S. Srinivasula,et al.  In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[12]  A. Chinnaiyan,et al.  The CED-3/ICE-like Protease Mch2 Is Activated during Apoptosis and Cleaves the Death Substrate Lamin A* , 1996, The Journal of Biological Chemistry.

[13]  A. Chinnaiyan,et al.  ICE-LAP6, a Novel Member of the ICE/Ced-3 Gene Family, Is Activated by the Cytotoxic T Cell Protease Granzyme B* , 1996, The Journal of Biological Chemistry.

[14]  D. Chan,et al.  DNA‐dependent protein kinase catalytic subunit: a target for an ICE‐like protease in apoptosis. , 1996, The EMBO journal.

[15]  N. Thornberry,et al.  The three-dimensional structure of apopain/CPP32, a key mediator of apoptosis , 1996, Nature Structural Biology.

[16]  Matthias Mann,et al.  FLICE, A Novel FADD-Homologous ICE/CED-3–like Protease, Is Recruited to the CD95 (Fas/APO-1) Death-Inducing Signaling Complex , 1996, Cell.

[17]  D. Livingston,et al.  INTERLEUKIN-1β CONVERTING ENZYME INHIBITION BLOCKS PROGRESSION OF TYPE II COLLAGEN-INDUCED ARTHRITIS IN MICE , 1996 .

[18]  H. Horvitz,et al.  The Caenorhabditis elegans cell-death protein CED-3 is a cysteine protease with substrate specificities similar to those of the human CPP32 protease. , 1996, Genes & development.

[19]  S. Nagata,et al.  Sequential activation of ICE-like and CPP32-like proteases during Fas-mediated apoptosis , 1996, Nature.

[20]  J. Mankovich,et al.  Protease Activity of in Vitro Transcribed and Translated Caenorhabditis elegans Cell Death Gene (ced-3) Product (*) , 1996, The Journal of Biological Chemistry.

[21]  P. Caron,et al.  Identification and Characterization of CPP32/Mch2 Homolog 1, a Novel Cysteine Protease Similar to CPP32 (*) , 1996, The Journal of Biological Chemistry.

[22]  A. Chinnaiyan,et al.  ICE-LAP3, a Novel Mammalian Homologue of the Caenorhabditis elegans Cell Death Protein Ced-3 Is Activated during Fas- and Tumor Necrosis Factor-induced Apoptosis (*) , 1996, The Journal of Biological Chemistry.

[23]  E. Alnemri,et al.  Mch3, a novel human apoptotic cysteine protease highly related to CPP32. , 1995, Cancer research.

[24]  R. Weichselbaum,et al.  Proteolytic activation of protein kinase C delta by an ICE‐like protease in apoptotic cells. , 1995, The EMBO journal.

[25]  C. Schneider,et al.  Microfilament reorganization during apoptosis: the role of Gas2, a possible substrate for ICE‐like proteases. , 1995, The EMBO journal.

[26]  B. Grasberger,et al.  Production, purification, and crystallization of human interleukin‐1β converting enzyme derived from an Escherichia coli expression system , 1995, Protein science : a publication of the Protein Society.

[27]  J. Mankovich,et al.  Inhibition of ICE family proteases by baculovirus antiapoptotic protein p35. , 1995, Science.

[28]  H. Horvitz,et al.  Inhibition of the Caenorhabditis elegans cell-death protease CED-3 by a CED-3 cleavage site in baculovirus p35 protein , 1995, Nature.

[29]  M. Su,et al.  Cleavage of Poly(ADP-ribose) Polymerase by Interleukin-1β Converting Enzyme and Its Homologs TX and Nedd-2 (*) , 1995, The Journal of Biological Chemistry.

[30]  C. Slaughter,et al.  Purification of an Interleukin-1 Converting Enzyme-related Cysteine Protease That Cleaves Sterol Regulatory Element-binding Proteins between the Leucine Zipper and Transmembrane Domains (*) , 1995, The Journal of Biological Chemistry.

[31]  Patrick R. Griffin,et al.  Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis , 1995, Nature.

[32]  E. Alnemri,et al.  Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family. , 1995, Cancer research.

[33]  S. Molineaux,et al.  Molecular Cloning and Pro-apoptotic Activity of ICErelII and ICErelIII, Members of the ICE/CED-3 Family of Cysteine Proteases (*) , 1995, The Journal of Biological Chemistry.

[34]  J. Mankovich,et al.  Identification and Characterization of ICH-2, a Novel Member of the Interleukin-1β-converting Enzyme Family of Cysteine Proteases (*) , 1995, The Journal of Biological Chemistry.

[35]  Muneesh Tewari,et al.  Yama/CPP32β, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase , 1995, Cell.

[36]  L. Révész,et al.  Reduction of inflammation and pyrexia in the rat by oral administration of SDZ 224‐015, an inhibitor of the interleukin‐1β converting enzyme , 1995, British journal of pharmacology.

[37]  M. Su,et al.  A novel human protease similar to the interleukin‐1 beta converting enzyme induces apoptosis in transfected cells. , 1995, The EMBO journal.

[38]  J. Camonis,et al.  A Novel Protein That Interacts with the Death Domain of Fas/APO1 Contains a Sequence Motif Related to the Death Domain (*) , 1995, The Journal of Biological Chemistry.

[39]  M. Su,et al.  Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme. , 1995, Science.

[40]  N. Thornberry,et al.  A synthetic inhibitor of interleukin-1 beta converting enzyme prevents endotoxin-induced interleukin-1 beta production in vitro and in vivo. , 1995, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[41]  K. Amrein,et al.  Purification and characterization of recombinant human p50csk protein-tyrosine kinase from an Escherichia coli expression system overproducing the bacterial chaperones GroES and GroEL. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[42]  R. Kamen,et al.  Mice deficient in IL-1β-converting enzyme are defective in production of mature IL-1β and resistant to endotoxic shock , 1995, Cell.

[43]  R. Dolle,et al.  Inhibition of mature IL-1 beta production in murine macrophages and a murine model of inflammation by WIN 67694, an inhibitor of IL-1 beta converting enzyme. , 1995, Journal of immunology.

[44]  E. Alnemri,et al.  CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. , 1994, The Journal of biological chemistry.

[45]  Y. Lazebnik,et al.  Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE , 1994, Nature.

[46]  Douglas K. Miller,et al.  IL-1 beta-converting enzyme is present in monocytic cells as an inactive 45-kDa precursor. , 1994, Journal of immunology.

[47]  L. Wang,et al.  Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death , 1994, Cell.

[48]  J. Mankovich,et al.  Crystal structure of the cysteine protease interleukin-1β-converting enzyme: A (p20/p10)2 homodimer , 1994, Cell.

[49]  Mark A. Murcko,et al.  Structure and mechanism of interleukin-lβ converting enzyme , 1994, Nature.

[50]  M. Fishman,et al.  Prevention of vertebrate neuronal death by the crmA gene. , 1994, Science.

[51]  Shai Shaham,et al.  The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme , 1993, Cell.

[52]  K. O. Elliston,et al.  A novel heterodimeric cysteine protease is required for interleukin-1βprocessing in monocytes , 1992, Nature.

[53]  C. March,et al.  Molecular cloning of the interleukin-1 beta converting enzyme. , 1992, Science.

[54]  J. Weidner,et al.  IL-1-converting enzyme requires aspartic acid residues for processing of the IL-1 beta precursor at two distinct sites and does not cleave 31-kDa IL-1 alpha. , 1991, Journal of immunology.

[55]  R. Black,et al.  Substrate specificity of the protease that processes human interleukin-1 beta. , 1990, The Journal of biological chemistry.

[56]  P. Cameron,et al.  Identification of a monocyte specific pre-interleukin 1 beta convertase activity. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[57]  R. Black,et al.  Activation of interleukin‐ 1β by a co‐induced protease , 1989 .

[58]  Irwin A. Rose,et al.  Enzyme structure and mechanism (2nd edn): by Alan Fersht, W. H. Freeman & Co., 1985. £14.95 pbk, £28.95 hbk (xxi + 475 pages) ISBN 0 7167 1615 1 , 1985 .

[59]  C. Jackson,et al.  Solution composition dependent variation in extinction coefficients for p-nitroaniline. , 1983, Biochimica et biophysica acta.

[60]  A. C. Chang,et al.  Construction and characterization of amplifiable multicopy DNA cloning vehicles derived from the P15A cryptic miniplasmid , 1978, Journal of bacteriology.

[61]  A. Fersht.  Enzyme structure and mechanism , 1977 .

[62]  H. Edelhoch,et al.  Spectroscopic determination of tryptophan and tyrosine in proteins. , 1967, Biochemistry.