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Essential Contribution Of Caspase 3/CPP32 To Apoptosis And Its Associated Nuclear Changes.
M. Woo, R. Hakem, M. Soengas, G. Duncan, A. Shahinian, D. Kägi, A. Hakem, M. McCurrach, W. Khoo, S. Kaufman, G. Senaldi, T. Howard, S. Lowe, T. W. Mak
Published 1998 · Biology, Medicine
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Caspases are fundamental components of the mammalian apoptotic machinery, but the precise contribution of individual caspases is controversial. CPP32 (caspase 3) is a prototypical caspase that becomes activated during apoptosis. In this study, we took a comprehensive approach to examining the role of CPP32 in apoptosis using mice, embryonic stem (ES) cells, and mouse embryonic fibroblasts (MEFs) deficient for CPP32. CPP32(ex3-/-) mice have reduced viability and, consistent with an earlier report, display defective neuronal apoptosis and neurological defects. Inactivation of CPP32 dramatically reduces apoptosis in diverse settings, including activation-induced cell death (AICD) of peripheral T cells, as well as chemotherapy-induced apoptosis of oncogenically transformed CPP32(-/-) MEFs. As well, the requirement for CPP32 can be remarkably stimulus-dependent: In ES cells, CPP32 is necessary for efficient apoptosis following UV- but not gamma-irradiation. Conversely, the same stimulus can show a tissue-specific dependence on CPP32: Hence, TNFalpha treatment induces normal levels of apoptosis in CPP32 deficient thymocytes, but defective apoptosis in oncogenically transformed MEFs. Finally, in some settings, CPP32 is required for certain apoptotic events but not others: Select CPP32(ex3-/-) cell types undergoing cell death are incapable of chromatin condensation and DNA degradation, but display other hallmarks of apoptosis. Together, these results indicate that CPP32 is an essential component in apoptotic events that is remarkably system- and stimulus-dependent. Consequently, drugs that inhibit CPP32 may preferentially disrupt specific forms of cell death.
This paper references
The Caenorhabditis elegans cell-death protein CED-3 is a cysteine protease with substrate specificities similar to those of the human CPP32 protease.
D. Xue (1996)
Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a
M. Serrano (1997)
Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures
C. A. Smith (1989)
C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2
M. Hengartner (1994)
Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages.
V. Fadok (1992)
Selective induction of p53 and chemosensitivity in RB-deficient cells by E1A mutants unable to bind the RB-related proteins.
A. Samuelson (1997)
Programmed cell death in invertebrates.
M. Hengartner (1996)
A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia
M. Kastan (1992)
Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours
T. Graeber (1996)
A Combinatorial Approach Defines Specificities of Members of the Caspase Family and Granzyme B
N. Thornberry (1997)
Interleukin-1 beta converting enzyme.
N. Thornberry (1994)
Cleavage of CPP32 by Granzyme B Represents a Critical Role for Granzyme B in the Induction of Target Cell DNA Fragmentation*
A. Darmon (1996)
The killer and the executioner: how apoptosis controls malignancy.
D. Green (1995)
The molecular biology of apoptosis.
D. Vaux (1996)
Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis
D. Nicholson (1995)
T‐cell receptor ligation by peptide/MHC induces activation of a caspase in immature thymocytes: the molecular basis of negative selection
L. K. Clayton (1997)
Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract
Y. Goldberg (1996)
Mechanisms and genes of cellular suicide
H. Steller (1995)
Death-defying acts: a meeting review on apoptosis.
E. White (1993)
p53 and its 14 kDa C-terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches
S. Lee (1995)
P. W. Mesner (1997)
bax-deficiency promotes drug resistance and oncogenic transformation by attenuating p53-dependent apoptosis.
M. McCurrach (1997)
In vivo regulation of rat neutrophil apoptosis occurring spontaneously or induced with TNF-alpha or cycloheximide.
H. Tsuchida (1995)
ICE-LAP6, a Novel Member of the ICE/Ced-3 Gene Family, Is Activated by the Cytotoxic T Cell Protease Granzyme B*
H. Duan (1996)
CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme.
T. Fernandes-Alnemri (1994)
Programmed cell death in Caenorhabditis elegans.
M. Hengartner (1994)
p53 is required for radiation-induced apoptosis in mouse thymocytes
S. Lowe (1993)
Elimination of self-reactive B lymphocytes proceeds in two stages: Arrested development and cell death
S. Hartley (1993)
Cell‐free reconstitution of Fas‐, UV radiation‐ and ceramide‐induced apoptosis.
S. J. Martin (1995)
Sensitive method for measuring apoptosis and cell surface phenotype in human thymocytes by flow cytometry.
I. Schmid (1994)
Human ICE/CED-3 Protease Nomenclature
E. Alnemri (1996)
Apaf-1, a Human Protein Homologous to C. elegans CED-4, Participates in Cytochrome c–Dependent Activation of Caspase-3
H. Zou (1997)
ICE-related proteases in apoptosis.
A. Takahashi (1996)
Proteolytic activation of the cell death protease Yama/CPP32 by granzyme B.
L. T. Quan (1996)
Double identity for proteins of the Bcl-2 family
John Calvin Reed (1997)
A cysteine protease inhibitor prevents activation-induced T-cell apoptosis and death of peripheral blood cells from human immunodeficiency virus-infected individuals by inhibiting upregulation of Fas ligand.
Y. Yang (1997)
DFF, a Heterodimeric Protein That Functions Downstream of Caspase-3 to Trigger DNA Fragmentation during Apoptosis
X. Liu (1997)
Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice
K. Kuida (1996)
p53-dependent apoptosis modulates the cytotoxicity of anticancer agents
S. Lowe (1993)
Baculovirus p35 prevents developmentally programmed cell death and rescues a ced‐9 mutant in the nematode Caenorhabditis elegans.
A. Sugimoto (1994)
Membrane and morphological changes in apoptotic cells regulated by caspase-mediated activation of PAK2.
T. Rudel (1997)
Cytotoxic T-cell-derived granzyme B activates the apoptotic protease ICE-LAP3
A. Chinnaiyan (1996)
p53-independent apoptosis induced by paclitaxel through an indirect mechanism.
J. S. Lanni (1997)
Fas-induced Activation of the Cell Death-related Protease CPP32 Is Inhibited by Bcl-2 and by ICE Family Protease Inhibitors*
R. Armstrong (1996)
Thymocyte apoptosis induced by p53-dependent and independent pathways
A. Clarke (1993)
Multiple species of CPP32 and Mch2 are the major active caspases present in apoptotic cells
L. Faleiro (1997)
Stress-signalling kinase Sek1 protects thymocytes from apoptosis mediated by CD95 and CD3
H. Nishina (1997)
Apoptosis – role in infection and inflammation
W. Liles (1997)
Apopain/CPP32 cleaves proteins that are essential for cellular repair: a fundamental principle of apoptotic death
L. Casciola-Rosen (1996)
Apoptosis by Death Factor
S. Nagata (1997)
Apoptosis: molecular regulation of cell death.
A. Hale (1996)
Prevention of apoptosis by a baculovirus gene during infection of insect cells.
R. Clem (1991)
The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme
J. Yuan (1993)
Yama/CPP32β, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase
M. Tewari (1995)
Apoptosis in the pathogenesis and treatment of disease
C. Thompson (1995)
Activation of the apoptotic protease CPP32 by cytotoxic T-cell-derived granzyme B
A. Darmon (1995)
Cellular environments and apoptosis: tissue microenvironments control activated T-cell death.
A. Akbar (1997)
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Miao-Ju Chen (2010)
Neuroprotective effects of neuregulin-1 in rat models of focal cerebral ischemia
Wen-Ping Guo (2006)
Mouse models of cell death
A. M. Ranger (2001)
Macrophage-mediated clearance of cells undergoing caspase-3-independent death
C. Turner (2003)
Apoptosis During Thymocyte Development Caspase Enzyme Activity Is Not Essential for Perlmutter
Petra Doerfler (2000)
Reduced pulmonary function is age-dependent in the rat lung in normoxia
G. Petruccelli (2010)
Genetic disorders of programmed cell death in the immune system.
N. Bidère (2006)
Regional Differences in the Temporal Expression of Non-Apoptotic Caspase-3-Positive Bergmann Glial Cells in the Developing Rat Cerebellum
V. Finckbone (2009)
Synthesis, characterization and biological evaluation of some new indomethacin analogs with a colon tumor cell growth inhibitory activity
S. I. Eissa (2017)
Paracrine control of tissue regeneration and cell proliferation by Caspase-3
K. Boland (2013)
Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development.
W. Yeh (2000)
Tumor-induced apoptosis of T lymphocytes: elucidation of intracellular apoptotic events.
B. Gastman (2000)
Degeneration of the neuromuscular synaptic compartment in normal and Wlds mutant mice
T. Gillingwater (2002)
Regulation of biochemical and morphological features of chemical- and receptor-mediated apoptosis in Jurkat T cells
V. L. Johnson (2000)
Absence of caspase-3 protects against denervation-induced skeletal muscle atrophy.
P. Plant (2009)
Sall2 is required for proapoptotic Noxa expression and genotoxic stress-induced apoptosis by doxorubicin
D. Escobar (2015)
Does the plant mitochondrion integrate cellular stress and regulate programmed cell death
J. E. Taylor (2000)
Ionizing radiation but not anticancer drugs causes cell cycle arrest and failure to activate the mitochondrial death pathway in MCF-7 breast carcinoma cells
R. Jänicke (2001)
Porphyromonas gingivalis gingipains cause defective macrophage migration towards apoptotic cells and inhibit phagocytosis of primary apoptotic neutrophils
S. A. Castro (2017)
The role of Pten/Akt signaling pathway involved in BPA‐induced apoptosis of rat sertoli cells
C. Wang (2015)
Biochemical and Molecular Actions of Nutrients N-Acetylcysteine , Vitamin C and Vitamin E Diminish Homocysteine Thiolactone – Induced Apoptosis in Human Promyeloid HL-60 Cells 1
R. Huang (2002)
Human urine extract CDA-2 induces apoptosis of myelodysplastic syndrome-derived MUTZ-1 cells through the PI3K/Akt signaling pathway in a caspase-3-dependent manner
J. Huang (2008)
Impaired caspase-3 expression by peripheral T cells in chronic autoimmune thyroiditis and in autoimmune polyendocrine syndrome-2.
F. Vendrame (2006)
Suberoylanilide Hydroxamic Acid as a Potential Therapeutic Agent for Human Breast Cancer Treatment
L. Huang (2000)
Cloning and functional characterization of the murine caspase-3 gene promoter.
L. Sabbagh (2006)
Role of Proteases in the Pathophysiology of Neurodegenerative Diseases
A. Lajtha (2002)
Mutant huntingtin induced transfected PC12 cell death by overload of cholesterol.
Shang-zhi Xu (2011)
Brain dysfunction and cell death in type 2 diabetes : A neuroprotective role for the peripheral treatment with Exendin-4
Inês Sebastião (2014)
Self-Assembled Peptide-Lanthanide Nanoclusters for Safe Tumor Therapy: Overcoming and Utilizing Biological Barriers to Peptide Drug Delivery.
J. Yan (2018)
In situ immunodetection of activated caspase-3 in apoptotic neurons in the developing nervous system
A. Srinivasan (1998)
Detecting and quantifying apoptosis in tissue sections.
V. Save (2004)
The incidence of apoptosis after IVF with morphologically abnormal bovine spermatozoa.
A. Walters (2005)See more