Open Access
Mammalian caspases: structure ,a ctivation ,s ubstrates, and functions during apoptosis
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
MLN4924 induces Noxa upregulation in acute myelogenous leukemia and synergizes with Bcl-2 inhibitors
Katherine L. B. Knorr,Paula A. Schneider,Xue Wei Meng,Haiming Dai,B D Smith,Allan D. Hess,Judith E. Karp,Scott H. Kaufmann,Scott H. Kaufmann +8 more
TL;DR: It is demonstrated that MLN 4924 induces apoptosis in AML cell lines and clinical samples via a mechanism distinct from those observed in other malignancies, and new insight is provided into MLN4924-induced engagement of the apoptotic machinery that could help guide further exploration of MLN4824 for AML.
Journal ArticleDOI
SIRT1-mediated FoxOs pathways protect against apoptosis by promoting autophagy in osteoblast-like MC3T3-E1 cells exposed to sodium fluoride.
TL;DR: SIRT1-inducedAutophagy enhancement protects against fluoride-induced apoptosis through autophagy induction in MC3T3-E1 cells, which may be associated with a SIRT1 -FoxO1-Rab7 axis and a Sirt1-FoxO3-Binp3 axis.
Journal ArticleDOI
Functional characterization of SAG/RBX2/ROC2/RNF7, an antioxidant protein and an E3 ubiquitin ligase
TL;DR: Given its major role in promoting targeted degradation of tumor suppressive proteins, leading to apoptosis suppression and accelerated tumorigenesis, SAG E3 ligase appears to be an attractive anticancer target.
Journal ArticleDOI
Activators of the Epstein-Barr Virus Lytic Program Concomitantly Induce Apoptosis, but Lytic Gene Expression Protects from Cell Death
TL;DR: Protection from apoptosis was associated with the presence of the EBV genome and treatment with phosphonoacetic acid or acyclovir prior to induction with PMA, anti-Ig, or TGF-β blocked the protective effect in Mutu-I cells.
Journal ArticleDOI
Ataxin-3 protein and RNA toxicity in spinocerebellar ataxia type 3: current insights and emerging therapeutic strategies.
TL;DR: The functioning of ataxin-3 and the involvement of known protein and RNA toxicity mechanisms of mutant ataxIn-3 that have been discovered are reviewed, as well as future opportunities for therapeutic intervention.
References
More filters
Journal ArticleDOI
The neighbor-joining method: a new method for reconstructing phylogenetic trees.
Naruya Saitou,Masatoshi Nei +1 more
TL;DR: The neighbor-joining method and Sattath and Tversky's method are shown to be generally better than the other methods for reconstructing phylogenetic trees from evolutionary distance data.
Journal ArticleDOI
The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools.
TL;DR: ClUSTAL X is a new windows interface for the widely-used progressive multiple sequence alignment program CLUSTAL W, providing an integrated system for performing multiple sequence and profile alignments and analysing the results.
Book ChapterDOI
Cell death : the significance of apoptosis
TL;DR: It has proved feasible to categorize most if not all dying cells into one or the other of two discrete and distinctive patterns of morphological change, which have, generally, been found to occur under disparate but individually characteristic circumstances.
Journal ArticleDOI
The biochemistry of apoptosis
TL;DR: The basic components of the death machinery are reviewed, how they interact to regulate apoptosis in a coordinated manner is described, and the main pathways that are used to activate cell death are discussed.
Journal ArticleDOI
Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade
Peng Li,Deepak Nijhawan,Imawati Budihardjo,Srinivasa M. Srinivasula,Manzoor Ahmad,Emad S. Alnemri,Xiaodong Wang +6 more
TL;DR: Mutation of the active site of caspase-9 attenuated the activation of cazase-3 and cellular apoptotic response in vivo, indicating that casp enzyme-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP.