Suicidal Tendencies: Apoptotic Cell Death by Caspase Family Proteinases*

Certain proteases are not merely degradative enzymes but are highly regulated signaling molecules that control critical biological processes via specific limited proteolysis. Caspase proteinases and their central role in apoptotic cell death provide a prime example of this concept. These cysteine proteinases exist as latent zymogens; however, once activated by apoptotic signals, they systematically dismantle and package the cell by cleaving key cellular proteins solely after aspartate residues. Here we review caspase proteinases with an emphasis on their structure, activation, and critical role in the apoptotic mechanism.

[1]  Douglas K. Miller,et al.  Activation of the Native 45-kDa Precursor Form of Interleukin-1-converting Enzyme* , 1996, The Journal of Biological Chemistry.

[2]  Xiaodong Wang,et al.  Bid, a Bcl2 Interacting Protein, Mediates Cytochrome c Release from Mitochondria in Response to Activation of Cell Surface Death Receptors , 1998, Cell.

[3]  Stephen W. Fesik,et al.  NMR structure and mutagenesis of the FADD (Mort1) death-effector domain , 1998, Nature.

[4]  G. Salvesen,et al.  Activation of pro-caspase-7 by serine proteases includes a non-canonical specificity. , 1997, The Biochemical journal.

[5]  N. Thornberry,et al.  A Combinatorial Approach Defines Specificities of Members of the Caspase Family and Granzyme B , 1997, The Journal of Biological Chemistry.

[6]  J. Larrick,et al.  Purification of a 24-kD protease from apoptotic tumor cells that activates DNA fragmentation , 1994, The Journal of experimental medicine.

[7]  P. Libby,et al.  Ligation of CD40 Activates Interleukin 1β-converting Enzyme (Caspase-1) Activity in Vascular Smooth Muscle and Endothelial Cells and Promotes Elaboration of Active Interleukin 1β* , 1997, The Journal of Biological Chemistry.

[8]  V. Dixit,et al.  ERICE, a Novel FLICE-activatable Caspase* , 1998, The Journal of Biological Chemistry.

[9]  A. Malkinson,et al.  Calpain activation in apoptosis , 1994, Journal of cellular physiology.

[10]  J. Beckmann,et al.  Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally. , 1998, Immunity.

[11]  David Wallach,et al.  Involvement of MACH, a Novel MORT1/FADD-Interacting Protease, in Fas/APO-1- and TNF Receptor–Induced Cell Death , 1996, Cell.

[12]  N. Thornberry,et al.  Caspases: killer proteases. , 1997, Trends in biochemical sciences.

[13]  J C Reed,et al.  Caspase-9 Can Be Activated without Proteolytic Processing* , 1999, The Journal of Biological Chemistry.

[14]  H. Steller,et al.  DCP-1, a Drosophila Cell Death Protease Essential for Development , 1997, Science.

[15]  R. Siegel,et al.  Membrane Oligomerization and Cleavage Activates the Caspase-8 (FLICE/MACHα1) Death Signal* , 1998, The Journal of Biological Chemistry.

[16]  D. Baltimore,et al.  Essential role of CED-4 oligomerization in CED-3 activation and apoptosis. , 1998, Science.

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

[18]  Gerhard Wagner,et al.  Solution Structure of the RAIDD CARD and Model for CARD/CARD Interaction in Caspase-2 and Caspase-9 Recruitment , 1998, Cell.

[19]  Dale E. Bredesen,et al.  Caspase Cleavage of Gene Products Associated with Triplet Expansion Disorders Generates Truncated Fragments Containing the Polyglutamine Tract* , 1998, The Journal of Biological Chemistry.

[20]  D. Green,et al.  Dicing with death: dissecting the components of the apoptosis machinery. , 1994, Trends in biochemical sciences.

[21]  M. Hayden,et al.  Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract , 1996, Nature Genetics.

[22]  Vishva M. Dixit,et al.  RAIDD is a new 'death' adaptor molecule , 1997, Nature.

[23]  D. Nicholson,et al.  Activation of the apoptotic protease CPP32 by cytotoxic T-cell-derived granzyme B , 1995, Nature.

[24]  Stephen W. Fesik,et al.  NMR structure and mutagenesis of the Fas (APO-1/CD95) death domain , 1996, Nature.

[25]  V. Dixit,et al.  Fas-associated Death Domain Protein Interleukin-1β-converting Enzyme 2 (FLICE2), an ICE/Ced-3 Homologue, Is Proximally Involved in CD95- and p55-mediated Death Signaling* , 1997, The Journal of Biological Chemistry.

[26]  H. Horvitz,et al.  Genetic control of programmed cell death in the nematode C. elegans , 1986, Cell.

[27]  M. Moskowitz,et al.  Defects in regulation of apoptosis in caspase-2-deficient mice. , 1998, Genes & development.

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

[29]  David Smith,et al.  Involvement of Caspases in Proteolytic Cleavage of Alzheimer’s Amyloid-β Precursor Protein and Amyloidogenic Aβ Peptide Formation , 1999, Cell.

[30]  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.

[31]  E. Alnemri,et al.  The Baculovirus Anti-apoptotic p35 Protein Promotes Transformation of Mouse Embryo Fibroblasts* , 1998, The Journal of Biological Chemistry.

[32]  Yuanming Hu,et al.  Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[33]  J. Blenis,et al.  Caspase-8 Is Required for Cell Death Induced by Expanded Polyglutamine Repeats , 1999, Neuron.

[34]  B. Schwab,et al.  The novel SAR‐binding domain of scaffold attachment factor A (SAF‐A) is a target in apoptotic nuclear breakdown , 1997, The EMBO journal.

[35]  T. Sunderland,et al.  Participation of Presenilin 2 in Apoptosis: Enhanced Basal Activity Conferred by an Alzheimer Mutation , 1996, Science.

[36]  Junying Yuan,et al.  Murine Caspase-11, an ICE-Interacting Protease, Is Essential for the Activation of ICE , 1998, Cell.

[37]  C. Widmann,et al.  Caspase-dependent Cleavage of Signaling Proteins during Apoptosis , 1998, The Journal of Biological Chemistry.

[38]  Junying Yuan,et al.  Cleavage of BID by Caspase 8 Mediates the Mitochondrial Damage in the Fas Pathway of Apoptosis , 1998, Cell.

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

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

[41]  Margot Thome,et al.  Inhibition of death receptor signals by cellular FLIP , 1997, Nature.

[42]  T. Ley,et al.  Natural killer and lymphokine-activated killer cells require granzyme B for the rapid induction of apoptosis in susceptible target cells. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[43]  J C Reed,et al.  Pro-caspase-3 Is a Major Physiologic Target of Caspase-8* , 1998, The Journal of Biological Chemistry.

[44]  G M Cohen,et al.  Caspases: the executioners of apoptosis. , 1997, The Biochemical journal.

[45]  Seamus J. Martin,et al.  Protease activation during apoptosis: Death by a thousand cuts? , 1995, Cell.

[46]  W. Fiers,et al.  Characterization of seven murine caspase family members , 1997, FEBS letters.

[47]  S. Srinivasula,et al.  Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization. , 1998, Molecular cell.

[48]  P. Bucher,et al.  The CARD domain: a new apoptotic signalling motif. , 1997, Trends in biochemical sciences.

[49]  G. Kroemer,et al.  Proteasome activation occurs at an early, premitochondrial step of thymocyte apoptosis. , 1998, Journal of immunology.

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

[51]  V. Dixit,et al.  Death receptors: signaling and modulation. , 1998, Science.

[52]  V. Cryns,et al.  Proteases to die for. , 1998, Genes & development.

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

[54]  D. Green.  Apoptotic Pathways The Roads to Ruin , 1998, Cell.

[55]  M. Grütter,et al.  Structure of Recombinant Human CPP32 in Complex with the Tetrapeptide Acetyl-Asp-Val-Ala-Asp Fluoromethyl Ketone* , 1997, The Journal of Biological Chemistry.

[56]  Brent R. Stockwell,et al.  An Induced Proximity Model for Caspase-8 Activation* , 1998, The Journal of Biological Chemistry.

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

[58]  D. Baltimore,et al.  Autoproteolytic activation of pro-caspases by oligomerization. , 1998, Molecular cell.

[59]  F. Martinon,et al.  Identification of CARDIAK, a RIP-like kinase that associates with caspase-1 , 1998, Current Biology.

[60]  S. Srinivasula,et al.  Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade , 1997, Cell.

[61]  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.

[62]  S. Srinivasula,et al.  CRADD, a novel human apoptotic adaptor molecule for caspase-2, and FasL/tumor necrosis factor receptor-interacting protein RIP. , 1997, Cancer research.

[63]  G. Salvesen,et al.  Caspase-14 Is a Novel Developmentally Regulated Protease* , 1998, The Journal of Biological Chemistry.

[64]  A. Kimchi,et al.  Cathepsin D protease mediates programmed cell death induced by interferon‐gamma, Fas/APO‐1 and TNF‐alpha. , 1996, The EMBO journal.