The CD95(APO-1/Fas) DISC and beyond

Marynen, Peter; Krammer, Peter H.

doi:10.1038/sj.cdd.4401186

Cited by 995 publications

(772 citation statements)

References 121 publications

Supporting

Mentioning

759

Contrasting

Unclassified

Order By: Relevance

“…The mechanism of activation of these initiator caspases depends critically on the engagement and activation of recruitment platforms such as the deathinducing signaling complex for caspase-8 and caspase-10, the PIDDosome for caspase-2 and the well-described apoptosome, for caspase-9. [48][49][50] These recruitment platforms integrate cellular signals, promote dimerization of initiator caspases and lead to the formation of an active enzyme proficient to initiate specific signaling cascades. 51,52 These platforms are multiprotein complexes consisting of various molecules assembled on a central scaffold protein that characteristically possesses three main domains: a region involved in ligand sensing, a domain driving oligomerization and a domain involved in recruiting the caspases.…”

Section: Activation Of Inflammatory Caspases: Inflammasomes and Othermentioning

confidence: 99%

Inflammatory caspases and inflammasomes: master switches of inflammation

2006

View full text Add to dashboard Cite

Fifteen years have passed since the cloning and characterization of the interleukin-1b-converting enzyme (ICE/caspase-1), the first identified member of a family of proteases currently known as caspases. Caspase-1 is the prototypical member of a subclass of caspases involved in cytokine maturation termed inflammatory caspases that also include caspase-4 caspase -5, caspase -11 and caspase -12. Efforts to elucidate the molecular mechanisms involved in the activation of these proteases have uncovered an important role for the NLR family members, NALPs, NAIP and IPAF. These proteins promote the assembly of multiprotein complexes termed inflammasomes, which are required for activation of inflammatory caspases. This article will review some evolutionary aspects, biochemical evidences and genetic studies, underlining the role of inflammasomes and inflammatory caspases in innate immunity against pathogens, autoinflammatory syndromes and in the biology of reproduction. Inflammatory CaspasesThe history of caspases began with the identification of an aspartate-specific protease activity involved in the conversion of the 31 kDa proIL-1b precursor to its active 17 kDa biologically active form, 1,2 and the identification of caspase-1 as the protease responsible for proIL-1b maturation. 3,4 The subsequent discovery of ced-3, that shares similarities with caspase-1 and which is involved in programmed cell death (PCD) in Caenorhabditis elegans, suggested that caspases might play fundamental roles in apoptosis. 5 As reviewed in the papers accompanying this issue of Cell Death and Differentiation, the role of apoptotic caspases in C. elegans and in vertebrates is crucial and deal with many facets of cell biology, development and diseases. In this review, we will focus on a subset of caspases present only in vertebrates and known as inflammatory caspases.Inflammatory caspases (also known as group I caspases) are encoded by three main genes in humans caspase-1, caspase-4 and caspase-5 and three main genes in mouse, caspase-1, caspase-11 and caspase-12. 6,7 In mammals, these caspases are characterized by the presence of a CARD domain at the N-terminus (Figure 1a). Human, chimp and mouse inflammatory caspases share significant similarity and are organized in a single locus (Figure 1c). Phylogenetic analysis of the conserved CARD domain suggests that the inflammatory caspases can be separated in evolutionaryrelated clusters (Figure 1b). The caspase-1 cluster contains caspase-1 and four other genes encoding decoy caspases: cop, inca1, inca2 and iceberg. These decoy caspase-1-like genes are absent in the mouse genome, suggesting that they have arisen recently by duplication of caspase-1. Although human and mouse caspase-1 are likely orthologues, sequence analysis suggests that human caspase-4 and caspase-5 have originated from a duplication of caspase-11. 7 However, the human caspase-12 gene, which in the chimp genome contains an SHG box important for it enzymatic activity, 8 evolved towards an enzymatically inactive form at some stage...

show abstract

Section: Activation Of Inflammatory Caspases: Inflammasomes and Othermentioning

confidence: 99%

Inflammatory caspases and inflammasomes: master switches of inflammation

2006

View full text Add to dashboard Cite

show abstract

“…CD95 (APO-1/Fas) belongs to the subfamily of death receptors, which is part of the TNF/nerve growth factorreceptor (NGF) superfamily. Upon stimulation of CD95 with its corresponding ligand CD95L (CD178), oligomerization of CD95 receptors leads to a conformational change and to formation of the DISC (death-inducing signaling complex) containing the adaptor FADD/ Mort1, pro-caspase-8, pro-caspase-10, and c-FLIP [7]. Recruitment of pro-caspase-8 to the DISC leads to its autoproteolytic activation and thereby to the start of a cascade of caspases [8].…”

Section: Introductionmentioning

confidence: 99%

In vitro generated human memory‐like T cells are CD95 type II cells and resistant towards CD95‐mediated apoptosis

et al. 2006

View full text Add to dashboard Cite

An adaptive immune response implies expansion of activated T cells and subsequent elimination to maintain homeostasis in a process called activation-induced cell death. Some cells, however, differentiate into memory cells and ensure a strong secondary immune response. To analyze the apoptosis phenotype of memory T cells on a cellular and molecular level, we have established an in vitro model of T cell activation and generation of cells phenotypically and functionally similar to memory cells. These longterm cultured T cells show a CD95-resistant phenotype, although they are still sensitive towards TCR/CD3-mediated apoptosis. Biochemical analysis revealed that these cells shift from CD95 type I (direct signaling from the receptor) during the effector phase to CD95 type II cells (dependent on the mitochondrial amplification loop). Moreover, their mitochondria are protected, probably due to high expression levels of Bcl-x L and Bcl-2. Thus, our data suggest a mechanism how memory T cells acquire resistance towards bystander cell death via the CD95 system.

show abstract

“…These results led Melino to propose that the ratio of TAp73 to DNp73 may dictate the response to chemotherapy and suggest that TAp73 is the oncologist's friend, whereas DNp73 may prove to be the foe in tumorigenesis. 11 Orchestration of cell death: a tale of death receptors and mitochondria Apoptosis can be induced either by activation of death receptors or by perturbation of mitochondria [12][13][14] (Figure 2). G Cohen (Leicester, UK) explained how the mitochondrial pathway can be engaged in response to death receptor signalling, facilitating apoptosis by release from the mitochondria of cytochrome c or the inhibitor of apoptosis (IAP) antagonists Smac/Diablo and Omi/HtrA2.…”

Section: A Complex Decision Of Life or Deathmentioning

confidence: 99%