← Back to Search
Caspase-3 Controls Both Cytoplasmic And Nuclear Events Associated With Fas-mediated Apoptosis In Vivo.
T. Zheng, S. Schlosser, T. Dao, R. Hingorani, I. N. Crispe, J. Boyer, R. Flavell
Published 1998 · Biology, Medicine
Save to my Library
Download PDFAnalyze on Scholarcy
Both caspase-1- and caspase-3-like activities are required for Fas-mediated apoptosis. However, the role of caspase-1 and caspase-3 in mediating Fas-induced cell death is not clear. We assessed the contributions of these caspases to Fas signaling in hepatocyte cell death in vitro. Although wild-type, caspase-1(-/-), and caspase-3(-/-) hepatocytes were killed at a similar rate when cocultured with FasL expressing NIH 3T3 cells, caspase-3(-/-) hepatocytes displayed drastically different morphological changes as well as significantly delayed DNA fragmentation. For both wild-type and caspase-1(-/-) apoptotic hepatocytes, typical apoptotic features such as cytoplasmic blebbing and nuclear fragmentation were seen within 6 hr, but neither event was observed for caspase-3(-/-) hepatocytes. We extended these studies to thymocytes and found that apoptotic caspase-3(-/-) thymocytes exhibited similar "abnormal" morphological changes and delayed DNA fragmentation observed in hepatocytes. Furthermore, the cleavage of various caspase substrates implicated in mediating apoptotic events, including gelsolin, fodrin, laminB, and DFF45/ICAD, was delayed or absent. The altered cleavage of these key substrates is likely responsible for the aberrant apoptosis observed in both hepatocytes and thymocytes deficient in caspase-3.
This paper references
Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis.
B. Soto (1997)
The Fas death factor
S. Nagata (1995)
A Combinatorial Approach Defines Specificities of Members of the Caspase Family and Granzyme B
N. Thornberry (1997)
Zheng et al
S. M. Laster (1998)
Fas Ligand-Induced Apoptosis as a Mechanism of Immune Privilege
T. Griffith (1995)
Protease activation during apoptosis: Death by a thousand cuts?
S. Martin (1995)
Murine Caspase-11, an ICE-Interacting Protease, Is Essential for the Activation of ICE
S. Wang (1998)
Studies of the lamin proteinase reveal multiple parallel biochemical pathways during apoptotic execution.
Y. Lazebnik (1995)
Caspases: the executioners of apoptosis.
G. Cohen (1997)
Proteolysis of Fodrin (Non-erythroid Spectrin) during Apoptosis (*)
S. J. Martin (1995)
Defects in regulation of apoptosis in caspase-2-deficient mice.
L. Bergeron (1998)
Apoptosis in the pathogenesis and treatment of disease
C. Thompson (1995)
Microfilament reorganization during apoptosis: the role of Gas2, a possible substrate for ICE‐like proteases.
C. Brancolini (1995)
Mice deficient in IL-1β-converting enzyme are defective in production of mature IL-1β and resistant to endotoxic shock
P. Li (1995)
A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD
M. Enari (1998)
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 (*)
H. Duan (1996)
Reduced Apoptosis and Cytochrome c–Mediated Caspase Activation in Mice Lacking Caspase 9
K. Kuida (1998)
A role for CD95 ligand in preventing graft rejection
D. Bellgrau (1995)
DFF, a Heterodimeric Protein That Functions Downstream of Caspase-3 to Trigger DNA Fragmentation during Apoptosis
X. Liu (1997)
Identification and Characterization of CPP32/Mch2 Homolog 1, a Novel Cysteine Protease Similar to CPP32 (*)
J. Lippke (1996)
Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme.
K. Kuida (1995)
Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice
K. Kuida (1996)
Cleavage of actin by interleukin 1 beta-converting enzyme to reverse DNase I inhibition.
C. Kayalar (1996)
Mch3, a novel human apoptotic cysteine protease highly related to CPP32.
T. Fernandes-Alnemri (1995)
Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis
H. Sakahira (1998)
Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes.
M. Woo (1998)
Specific resistance of T cells to CD95-induced apoptosis during S phase of the cell cycle.
T. Dao (1997)
Proteases to die for.
V. Cryns (1998)
Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis.
S. Kothakota (1997)
Caspase-3 Is Required for DNA Fragmentation and Morphological Changes Associated with Apoptosis*
R. Jänicke (1998)
Involvement of MACH, a Novel MORT1/FADD-Interacting Protease, in Fas/APO-1- and TNF Receptor–Induced Cell Death
M. Boldin (1996)
Sequential activation of ICE-like and CPP32-like proteases during Fas-mediated apoptosis
M. Enari (1996)
Mechanisms and genes of cellular suicide
H. Steller (1995)
FLICE, A Novel FADD-Homologous ICE/CED-3–like Protease, Is Recruited to the CD95 (Fas/APO-1) Death-Inducing Signaling Complex
M. Muzio (1996)
Tumor necrosis factor can induce both apoptic and necrotic forms of cell lysis.
S. Laster (1988)
CIDE, a novel family of cell death activators with homology to the 45 kDa subunit of the DNA fragmentation factor
N. Inohara (1998)
A License to Kill
A. Fraser (1996)
Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade
Peng Li (1997)
A naturally occurring soluble isoform of murine Fas generated by alternative splicing
D. Hughes (1995)
The Role of Fas in Autoimmune Diabetes
A. Chervonsky (1997)
Membrane and morphological changes in apoptotic cells regulated by caspase-mediated activation of PAK2.
T. Rudel (1997)
This paper is referenced by
Clearance of Dying Cells Galectin-1 T Cell Death Promotes Phagocytic CD 45-Mediated Fodrin Cleavage during
M. Pang (2009)
Normal Programmed Cell Death of Developing Avian and Mammalian Neurons Following Inhibition or Genetic Deletion of Caspases
R. Oppenheim (2001)
Macrophage-mediated clearance of cells undergoing caspase-3-independent death
C. Turner (2003)
Inhibition of poly (ADP-ribose) polymerase and caspase-3, but not caspase-1, prevents apoptosis and improves spatial memory of rats with twice-repeated cerebral ischemia.
Izzettin Hatip-Al-Khatib (2004)
Deficiency in caspase-9 or caspase-3 induces compensatory caspase activation
T. Zheng (2000)
Determining the roles of the intrinsic versus the extrinsic pathway in regulating neuronal programmed cell death in vivo.
A. Kanungo (2010)
Caspase Activity Is Involved in, but Is Dispensable for, Early Motoneuron Death in the Chick Embryo Cervical Spinal Cord
H. Yaginuma (2001)
Lymphoma Cells Activation and Apoptosis in WEHI 231 Receptor-Mediated Effector Caspase Activation Is Necessary for Antigen Mitochondria-Dependent Caspase-9
Cerebral signal transduction : from first to fourth messengers
M. Reith (2000)
RAD51 Plays a Crucial Role in Halting Cell Death Program Induced by Ionizing Radiation in Bovine Oocytes1
Loro L. Kujjo (2012)
Alterations in cell cycle and apoptosis in drug resistant cells
C. O’Loughlin (1999)
Effects of kinetin riboside on proliferation and proapoptotic activities in human normal and cancer cell lines
P. Dudzik (2011)
A mouse CD8 T cell-mediated acute autoimmune diabetes independent of the perforin and Fas cytotoxic pathways: possible role of membrane TNF.
P. Herrera (2000)
Expression of caspase family and muscle- and apoptosis-specific genes during skeletal myogenesis in mouse embryo.
T. Ikeda (2009)
Primary enamel knot cell death in Apaf-1 and caspase-9 deficient mice.
J. Setkova (2007)
Polyamine depletion switches the form of 2-deoxy-D-ribose-induced cell death from apoptosis to necrosis in HL-60 cells.
M. G. Monti (2004)
Bio-conjugate Approaches for Improved Targeted Toll-like receptor based Immune Adjuvant Vaccines
Katrin Kramer (2016)
Intracellular Stability of Anti-caspase-3 Intrabodies Determines Efficacy in Retargeting the Antigen*
A. Rajpal (2001)
Time sequence analysis of caspase-3-independent programmed cell death and apoptosis in X-irradiated human leukemic MOLT-4 cells
H. Nakano (2002)
Les rôles distincts des isoformes de myosine II non-musculaire dans des processus cellulaires impliquant le cytosquelette d'actine
Sara Solinet (2009)
Mitochondria-Dependent Caspase-9 Activation Is Necessary for Antigen Receptor-Mediated Effector Caspase Activation and Apoptosis in WEHI 231 Lymphoma Cells1
M. Herold (2002)
Serial killers: ordering caspase activation events in apoptosis
EA Slee (1999)
The circadian clock modulates anti-cancer properties of curcumin
Ashapurna Sarma (2016)
H2O2 at physiological concentrations modulates Leydig cell function inducing oxidative stress and apoptosis
D. Gautam (2005)
Caspase Deficiency: Involvement in Breast Carcinogenesis and Resistance
X. Yang (2001)
Is caspase-3 inhibition a valid therapeutic strategy in cerebral ischemia?
H. Loetscher (2001)
Reversion of autoimmune lymphoproliferative syndrome with an antimalarial drug: preliminary results of a clinical cohort study and molecular observations
J. van der Werff Ten Bosch (2002)
Tracing the accumulation and effects of mercury uptake in the previtellogenic ovary of crucian carp, Carassius auratus gibelio by autometallography and caspase-3 immunohistochemistry.
O. Zărnescu (2009)
Caspase-3-like activity determines the type of cell death following ionizing radiation in MOLT-4 human leukaemia cells
D. Coelho (2000)
Caspase 8 Activity in Membrane Blebs After Anti-Fas Ligation
B. Packard (2001)
Binding of multivalent CD147 phage induces apoptosis of U937 cells.
Nutjeera Intasai (2006)
Functional Validation of DownRegulated MicroRNAs in HeLa Cells Treated with Polyalthia longifolia Leaf Extract Using Different Microscopic Approaches: A Morphological Alteration-Based Validation.
Shanmugapriya (2019)See more