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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
More filters
Journal ArticleDOI
Structure and mechanism of interleukin-1 beta converting enzyme.
Wilson Keith P,J.A Black,John A. Thomson,Eunice E. Kim,James P. Griffith,Manuel A. Navia,Murcko Mark A,Stephen P. Chambers,R A Aldape,Scott A. Raybuck +9 more
TL;DR: The high-resolution structure of human ICE in complex with an inhibitor has been determined by X-ray diffraction and confirms the relationship between human ICE and cell-death proteins in other organisms.
Journal ArticleDOI
Apoptosis and interferons: role of interferon-stimulated genes as mediators of apoptosis.
Mamta Chawla-Sarkar,Daniel J. Lindner,Y-F Liu,Bryan R.G. Williams,Ganes C. Sen,Robert H. Silverman,Ernest C. Borden +6 more
TL;DR: Possible mechanisms and the role of ISGs involved in mediating apoptotic function of IFNs are emphasized.
Journal ArticleDOI
Disseminating the Genome: Joining, Resolving, and Separating Sister Chromatids During Mitosis and Meiosis
TL;DR: New research has identified proteins that hold sisters together while they are aligned on the metaphase plate and shed insight into the mechanisms that dissolve sister chromatid cohesion during both mitosis and meiosis.
Journal ArticleDOI
In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains.
Teresa Fernandes-Alnemri,Robert C. Armstrong,Joseph F. Krebs,Srinivasa M. Srinivasula,Lijuan Wang,Florencia Bullrich,Lawrence C. Fritz,Joseph A. Trapani,Kevin J. Tomaselli,Gerald Litwack,Emad S. Alnemri +10 more
TL;DR: The cloning of two novel ASCPs from human Jurkat T-lymphocytes are described, containing a QACQG pentapeptide instead of the QACRG present in ail known ASCPs, and the presence of the FADD-like domains in Mch4 and Mch5 suggests a role for these proteases in the Fas-apoptotic pathway.
Journal ArticleDOI
Cytochrome c: Can't Live with It—Can't Live without It
TL;DR: A first model predicts a specific channel located of cy tochrome c for oxidative phosphorylation in mitoin the outer membrane that allows release of cytochondria, where it assists with production of lifechrome c.