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Mammalian caspases: structure ,a ctivation ,s ubstrates, and functions during apoptosis
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TLDR
Caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases as discussed by the authors, and they play critical roles in initiation and execution of this process.Abstract:
■ Abstract Apoptosis is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli. Studies performed over the past 10 years have demonstrated that proteases play critical roles in initiation and execution of this process. The caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases. Caspases are synthesized as relatively inactive zymogens that become activated by scaffold-mediated transactivation or by cleavage via upstream proteases in an intracellular cascade. Regulation of caspase activation and activity occurs at several different levels: ( a) Zymogen gene transcription is regulated; ( b) antiapoptotic members of the Bcl-2 family and other cellular polypeptides block proximity-induced activation of certain procaspases; and ( c) certain cellular inhibitor of apoptosis proteins (cIAPs) can bind to and inhibit active caspases. Once activated, caspases cleave a variety of intracellular polypeptides, including major structural elements of the cytoplasm and nucleus, components of the DNA repair machinery, and a number of protein kinases. Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death.read more
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Caspase-3-Dependent Cleavage of the Glutamate-L-Cysteine Ligase Catalytic Subunit during Apoptotic Cell Death.
Christopher C. Franklin,Cecile M. Krejsa,Robert H. Pierce,Charles L. White,Nelson Fausto,Terrance J. Kavanagh +5 more
TL;DR: This report demonstrates that GCLC is a direct target for caspase-mediated cleavage in multiple models of apoptotic cell death and suggests that this post-translational modification may represent a novel mechanism for regulating GSH biosynthesis during apoptosis.
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Amphetamine induces apoptosis of medium spiny striatal projection neurons via the mitochondria-dependent pathway
TL;DR: Observations indicate that injections of doses of AMPH that are known to destroy striatal dopamine terminals can also cause apoptotic death of postsynaptic medium spiny projection neurons via mitochondria‐dependent mechanisms.
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Toxoplasma gondii inhibits Fas/CD95‐triggered cell death by inducing aberrant processing and degradation of caspase 8
Polya Vutova,Martina Wirth,Diana Hippe,Uwe Gross,Klaus Schulze-Osthoff,Ingo Schmitz,Carsten G. K. Lüder +6 more
TL;DR: Findings indicate that T. gondii aberrantly processes and finally degrades the initiator caspase 8, thereby, blocking Fas/CD95‐mediated apoptosis which signals independently of the apoptogenic function of host cell mitochondria.
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Characterization of Caspase Processing and Activation in HL-60 Cell Cytosol Under Cell-free Conditions NUCLEOTIDE REQUIREMENT AND INHIBITOR PROFILE
Peter W. Mesner,Keith C. Bible,Luis M. Martins,Timothy Kottke,Srinivasa M. Srinivasula,Phyllis A. Svingen,Tamie J. Chilcote,Guriq S. Basi,Jay S. Tung,Stan Krajewski,John C. Reed,Emad S. Alnemri,William C. Earnshaw,Scott H. Kaufmann +13 more
TL;DR: Results suggest that caspase-9 activation requires nucleotide hydrolysis and is inhibited by agents previously thought to affect apoptosis by other means.
Journal ArticleDOI
Interaction between XIAP and Smac/DIABLO in the Mouse Brain after Transient Focal Cerebral Ischemia
TL;DR: The results suggest that the XIAP pathway was activated upstream of the caspase cascade and that interaction among XIAP, Smac/DIABLO, and caspases plays an important role in the regulation of apoptotic neuronal cell death after transient focal cerebral ischemia.
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