Mechanisms of apoptosis.
TLDR
Knowledge of the molecular mechanisms of apoptosis is providing insights into the causes of multiple pathologies where aberrant cell death regulation occurs and is beginning to provide new approaches to the treatment of human diseases.Abstract:
Programmed cell death plays critical roles in a wide variety of physiological processes during fetal development and in adult tissues. In most cases, physiological cell death occurs by apoptosis as opposed to necrosis. Defects in apoptotic cell death regulation contribute to many diseases, including disorders where cell accumulation occurs (cancer, restenosis) or where cell loss ensues (stroke, heart failure, neurodegeneration, AIDS). In recent years, the molecular machinery responsible for apoptosis has been elucidated, revealing a family of intracellular proteases, the caspases, which are responsible directly or indirectly for the morphological and biochemical changes that characterize the phenomenon of apoptosis. Diverse regulators of the caspases have also been discovered, including activators and inhibitors of these cell death proteases. Inputs from signal transduction pathways into the core of the cell death machinery have also been identified, demonstrating ways of linking environmental stimuli to cell death responses or cell survival maintenance. Knowledge of the molecular mechanisms of apoptosis is providing insights into the causes of multiple pathologies where aberrant cell death regulation occurs and is beginning to provide new approaches to the treatment of human diseases.read more
Citations
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The role of apoptosis in response to photodynamic therapy: what, where, why, and how
TL;DR: The purpose of this review is to critically evaluate all of the recently published research on PDT-induced apoptosis, with a focus on studies providing mechanistic insights.
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Functional and physical interaction between Bcl‐XL and a BH3‐like domain in Beclin‐1
M. Chiara Maiuri,Gaetane Le Toumelin,Alfredo Criollo,Alfredo Criollo,Alfredo Criollo,Jean-Christophe Rain,Fabien Gautier,Philippe Juin,Ezgi Tasdemir,Ezgi Tasdemir,Ezgi Tasdemir,Gérard Pierron,Kostoula Troulinaki,Nektarios Tavernarakis,John A. Hickman,Olivier Geneste,Guido Kroemer,Guido Kroemer,Guido Kroemer +18 more
TL;DR: A novel autophagy‐stimulatory function of BH3‐only proteins beyond their established role as apoptosis inducers is revealed and is revealed by competitively disrupting the interaction between Beclin‐1 and B cl‐2 or Bcl‐XL.
Journal ArticleDOI
Structural biology of the Bcl-2 family of proteins.
TL;DR: The recently determined structure of the anti-apoptotic Bcl-w protein, the protein was also found to have a hydrophobic groove on its surface capable of binding BH3-containing proteins and peptides, which may explain why it is found predominately in the cytoplasm prior to activation.
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Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity
Wyndham H. Wilson,Owen A. O'Connor,Myron S. Czuczman,Ann S. LaCasce,John F. Gerecitano,John P. Leonard,Anil Tulpule,Kieron Dunleavy,Hao Xiong,Yi-Lin Chiu,Yue Cui,Todd A. Busman,Steven W. Elmore,Saul H. Rosenberg,Andrew Krivoshik,Sari H. Enschede,Rod A. Humerickhouse +16 more
TL;DR: Navitoclax showed a pharmacodynamic effect on circulating platelets and T cells and has a novel mechanism of peripheral thrombocytopenia and T-cell lymphopenia, attributable to high-affinity inhibition of Bcl-XL and BCL-2, respectively.
References
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Journal ArticleDOI
Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics.
TL;DR: Apoptosis seems to be involved in cell turnover in many healthy adult tissues and is responsible for focal elimination of cells during normal embryonic development, and participates in at least some types of therapeutically induced tumour regression.
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Mitochondria and apoptosis
Douglas R. Green,John C. Reed +1 more
TL;DR: A variety of key events in apoptosis focus on mitochondria, including the release of caspase activators (such as cytochrome c), changes in electron transport, loss of mitochondrial transmembrane potential, altered cellular oxidation-reduction, and participation of pro- and antiapoptotic Bcl-2 family proteins.
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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.
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Caspases: Enemies Within
TL;DR: This work has shown that understanding caspase regulation is intimately linked to the ability to rationally manipulate apoptosis for therapeutic gain.
Journal ArticleDOI
The Bcl-2 Protein Family: Arbiters of Cell Survival
Jerry M. Adams,Suzanne Cory +1 more
TL;DR: Bcl-2 and related cytoplasmic proteins are key regulators of apoptosis, the cell suicide program critical for development, tissue homeostasis, and protection against pathogens.