Fas Preassociation Required for Apoptosis Signaling and Dominant Inhibition by Pathogenic Mutations
30 Jun 2000-Science (American Association for the Advancement of Science)-Vol. 288, Iss: 5475, pp 2354-2357
TL;DR: Results show that formation of preassociated receptor complexes is necessary for Fas signaling and dominant interference in human disease.
Abstract: Heterozygous mutations encoding abnormal forms of the death receptor Fas dominantly interfere with Fas-induced lymphocyte apoptosis in human autoimmune lymphoproliferative syndrome. This effect, rather than depending on ligand-induced receptor oligomerization, was found to stem from ligand- independent interaction of wild-type and mutant Fas receptors through a specific region in the extracellular domain. Preassociated Fas complexes were found in living cells by means of fluorescence resonance energy transfer between variants of green fluorescent protein. These results show that formation of preassociated receptor complexes is necessary for Fas signaling and dominant interference in human disease.
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TL;DR: The identification of critical control points in the cell death pathway has yielded fundamental insights for basic biology, as well as provided rational targets for new therapeutics.
4,741 citations
Cites background from "Fas Preassociation Required for Apo..."
...Recent insight implicated defects in the ubiquitin pathway in somedeficiency (Chun et al., 2002; Siegel et al., 2000; Wang et al., 1999)....
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French Institute of Health and Medical Research1, Institut Gustave Roussy2, University of Paris-Sud3, University of Texas Southwestern Medical Center4, Thomas Jefferson University5, University of Massachusetts Medical School6, Roswell Park Cancer Institute7, Johns Hopkins University School of Medicine8, Penn State Milton S. Hershey Medical Center9, Goethe University Frankfurt10, St. Jude Children's Research Hospital11, University of Zurich12, University College London13, University of Adelaide14, South Australia Pathology15, Ludwig Institute for Cancer Research16, University of Graz17, Istituto Superiore di Sanità18, University of Michigan19, Northwestern University20, University of Rome Tor Vergata21, University of Cambridge22, University of Bern23, Ghent University24, Harvard University25, Karolinska Institutet26, University of Leicester27
TL;DR: A functional classification of cell death subroutines is proposed that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic programmed cell death, regulated necrosis, autophagic cell death and mitotic catastrophe.
Abstract: In 2009, the Nomenclature Committee on Cell Death (NCCD) proposed a set of recommendations for the definition of distinct cell death morphologies and for the appropriate use of cell death-related terminology, including 'apoptosis', 'necrosis' and 'mitotic catastrophe'. In view of the substantial progress in the biochemical and genetic exploration of cell death, time has come to switch from morphological to molecular definitions of cell death modalities. Here we propose a functional classification of cell death subroutines that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic apoptosis, regulated necrosis, autophagic cell death and mitotic catastrophe. Moreover, we discuss the utility of expressions indicating additional cell death modalities. On the basis of the new, revised NCCD classification, cell death subroutines are defined by a series of precise, measurable biochemical features.
2,238 citations
Cites background from "Fas Preassociation Required for Apo..."
...FAS subunits spontaneously assemble at the plasma membrane to generate trimers, owing to the so-called preligand assembly domain (PLAD).(31) Ligand binding stabilizes...
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TL;DR: Advances include the continued development of 'passive' markers for the measurement of biomolecule expression and localization in live cells, and 'active' indicators for monitoring more complex cellular processes such as small-molecule-messenger dynamics, enzyme activation and protein–protein interactions.
Abstract: Fluorescent probes are one of the cornerstones of real-time imaging of live cells and a powerful tool for cell biologists. They provide high sensitivity and great versatility while minimally perturbing the cell under investigation. Genetically-encoded reporter constructs that are derived from fluorescent proteins are leading a revolution in the real-time visualization and tracking of various cellular events. Recent advances include the continued development of 'passive' markers for the measurement of biomolecule expression and localization in live cells, and 'active' indicators for monitoring more complex cellular processes such as small-molecule-messenger dynamics, enzyme activation and protein-protein interactions.
1,895 citations
TL;DR: The role of CD95 (Apo-1/Fas)-mediated signalling in T-cell and B-cell development and during the course of an immune response and the understanding of the pathogenesis of diseases such as cancer, autoimmunity and AIDS is improved.
Abstract: Apoptosis in the immune system is a fundamental process regulating lymphocyte maturation, receptor repertoire selection and homeostasis Thus, death by apoptosis is as essential for the function of lymphocytes as growth and differentiation This article focuses on death receptor-associated apoptosis and the role of CD95 (Apo-1/Fas)-mediated signalling in T-cell and B-cell development and during the course of an immune response Gaining an insight into these processes improves our understanding of the pathogenesis of diseases such as cancer, autoimmunity and AIDS, and opens new approaches to rational treatment strategies
1,721 citations
Cites background from "Fas Preassociation Required for Apo..."
...To prevent the premature signalling of preassociated receptors, which is a dangerous situation, intracellular receptor-associated apoptosis blockers were postulate...
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TL;DR: Live cell imaging, in combination with photobleaching, energy transfer or fluorescence correlation spectroscopy are providing unprecedented insights into the movement of proteins and their interactions with cellular components.
Abstract: Since the advent of the green fluorescent protein, the subcellular localization, mobility, transport routes and binding interactions of proteins can be studied in living cells. Live cell imaging, in combination with photobleaching, energy transfer or fluorescence correlation spectroscopy are providing unprecedented insights into the movement of proteins and their interactions with cellular components. Remarkably, these powerful techniques are accessible to non-specialists using commercially available microscope systems.
1,213 citations
References
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TL;DR: Apoptosis is a cell suicide mechanism that enables metazoans to control cell number in tissues and to eliminate individual cells that threaten the animal's survival.
Abstract: Apoptosis is a cell suicide mechanism that enables metazoans to control cell number in tissues and to eliminate individual cells that threaten the animal's survival. Certain cells have unique sensors, termed death receptors, on their surface. Death receptors detect the presence of extracellular death signals and, in response, they rapidly ignite the cell's intrinsic apoptosis machinery.
5,968 citations
TL;DR: Findings suggest that FADD may play an important role in the proximal signal transduction of Fas, a mutant of Fas possessing enhanced killing activity, but not the functionally inactive mutants Fas-LPR and Fas-FD8.
2,555 citations
TL;DR: Caspases (cysteinyl aspartate-specific proteinases) mediate highly specific proteolytic cleavage events in dying cells, which collectively manifest the apoptotic phenotype.
2,480 citations
TL;DR: It is proposed that Yama may represent an effector component of the mammalian cell death pathway and suggest that CrmA blocks apoptosis by inhibiting Yama.
2,369 citations
TL;DR: The data suggest that in vivo CAP1–4 are the APO‐1 apoptosis‐transducing molecules.
Abstract: APO-1 (Fas/CD95), a member of the tumor necrosis factor receptor superfamily, induces apoptosis upon receptor oligomerization. In a search to identify intracellular signaling molecules coupling to oligomerized APO-1, several cytotoxicity-dependent APO-1-associated proteins (CAP) were immunoprecipitated from the apoptosis-sensitive human leukemic T cell line HUT78 and the lymphoblastoid B cell line SKW6.4. CAP1-3 (27-29 kDa) and CAP4 (55 kDa), instantly detectable after the crosslinking of APO-1, were associated only with aggregated (the signaling form of APO-1) and not with monomeric APO-1. CAP1 and CAP2 were identified as serine phosphorylated MORT1/FADD. The association of CAP1-4 with APO-1 was not observed with C-terminally truncated non-signaling APO-1. In addition, CAP1 and CAP2 did not associate with an APO-1 cytoplasmic tail carrying the lprcg amino acid replacement. Moreover, no APO-1-CAP association was found in the APO-1+, anti-APO-1-resistant pre-B cell line Boe. Our data suggest that in vivo CAP1-4 are the APO-1 apoptosis-transducing molecules.
2,253 citations