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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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References
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Anu Srinivasan,Feng Li,Angela M. Wong,Lalitha Kodandapani,Robert Smidt,Joseph F. Krebs,Lawrence C. Fritz,Joe C. Wu,Kevin J. Tomaselli +8 more
TL;DR: Data demonstrate that Bcl-xL can exert an anti-apoptotic function in cells in which caspase-8 is activated, and indicates that at least in some cells, casp enzyme-8 signaling in response to Fas or TNFR1 stimulation is regulated by a Bcl -xL-inhibitable step.
Journal ArticleDOI
Hydrogen peroxide induces apoptosis in HeLa cells through mitochondrial pathway.
TL;DR: It is demonstrated here, that in HeLa cells, apoptosis is triggered by H( 2)O(2) via the mitochondrial pathway involving upregulation of p73, and its downstream target Bax, and this was accompanied by up regulation of ERK, JNK, c-Myc, Hsp-70 and down regulation of anti-apoptotic Bcl-XL.
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Kinase cascades regulating entry into apoptosis.
TL;DR: Because individual kinase cascades can interact with one another, they are able to integrate conflicting exogenous stimuli and provide a link between cell surface receptors and the biochemical pathways leading to cell proliferation or cell death.
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TL;DR: Important questions that remain unsolved include the identity of the vertebrate IRP that triggers the apoptotic cascade and the identities of the crucial substrates whose cleavage results in the dramatic morphological changes during apoptosis.