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Article
Open AccessAuthor Correction: Endothelial activation of caspase-9 promotes neurovascular injury in retinal vein occlusion
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Article
Open AccessEndothelial activation of caspase-9 promotes neurovascular injury in retinal vein occlusion
Central nervous system ischemic injury features neuronal dysfunction, inflammation and breakdown of vascular integrity. Here we show that activation of endothelial caspase-9 after hypoxia-ischemia is a critica...
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Article
Exploring the prime site in caspases as a novel chemical strategy for understanding the mechanisms of cell death: a proof of concept study on necroptosis in cancer cells
Caspases participate in regulated cell death mechanisms and are divided into apoptotic and proinflammatory caspases. The main problem in identifying the unique role of a particular caspase in the mechanisms of...
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Article
Cytosolic Gram-negative bacteria prevent apoptosis by inhibition of effector caspases through lipopolysaccharide
The cytosolic appearance and propagation of bacteria cause overwhelming cellular stress responses that induce apoptosis under normal conditions. Therefore, successful bacterial colonization depends on the abil...
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Article
Potent and selective caspase-2 inhibitor prevents MDM-2 cleavage in reversine-treated colon cancer cells
Most caspases can be positioned unambiguously within the regulated cell death networks of apoptosis and pyroptosis, but the role of caspase-2, a highly conserved protease within the family, remains enigmatic. ...
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Article
Caspase selective reagents for diagnosing apoptotic mechanisms
Apical caspases initiate and effector caspases execute apoptosis. Reagents that can distinguish between caspases, particularly apical caspases-8, 9, and 10 are scarce and generally nonspecific. Based upon a pr...
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Article
Open AccessDetermination of extended substrate specificity of the MALT1 as a strategy for the design of potent substrates and activity-based probes
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) belongs to the CD clan of cysteine proteases. MALT1 is a unique enzyme among this clan because it recognizes the basic amino acid argi...
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Article
Synthesis of a HyCoSuL peptide substrate library to dissect protease substrate specificity
This protocol describes HyCoSuL, an approach that uses tetrapeptides containing natural and >100 unnatural amino acids to screen for protease substrate specificity and to engineer highly active and selective s...
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Article
Open AccessHighly sensitive and adaptable fluorescence-quenched pair discloses the substrate specificity profiles in diverse protease families
Internally quenched fluorescent (IQF) peptide substrates originating from FRET (Förster Resonance Energy Transfer) are powerful tool for examining the activity and specificity of proteases, and a variety of do...
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Article
Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling
Intracellular lipopolysaccharide from Gram-negative bacteria including Escherichia coli, Salmonella typhimurium, Shigella flexneri, and Burkholderia thailandensis activates mouse caspase-11, causing pyroptotic ce...
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Article
Open AccessA remarkable activity of human leukotriene A4 hydrolase (LTA4H) toward unnatural amino acids
Leukotriene A4 hydrolase (LTA4H––EC 3.3.2.6) is a bifunctional zinc metalloenzyme, which processes LTA4 through an epoxide hydrolase activity and is also able to trim one amino acid at a time from N-terminal pept...
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Article
Catalytic activity of the caspase-8–FLIPL complex inhibits RIPK3-dependent necrosis
Caspase-8 mediates apoptosis induced by 'death receptors' on the cell's surface. At the same time, it is able to prevent receptor interacting protein kinase (RIPK)-dependent necrosis. Without caspase-8, mice d...
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Protocol
N-Terminomics: A High-Content Screen for Protease Substrates and Their Cleavage Sites
Proteases play vital roles in many cellular processes and signaling cascades through specific limited cleavage of their targets. It is important to identify what proteins are substrates of proteases and where ...
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Article
Pannexin 1 channels mediate ‘find-me’ signal release and membrane permeability during apoptosis
Apoptotic cells were shown recently to discharge the nucleotides ATP and UTP to act as 'find-me' signals for phagocytes that engulf dying cells before they release potentially harmful cellular contents. This p...
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Article
Emerging principles in protease-based drug discovery
The development of new protease inhibitors has proved challenging in recent years. In their Perspective, Drag and Salvesen discuss the underlying reasons for this, and how lessons learned from failures can inf...
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Article
Targeting activated integrin αvβ3 with patient-derived antibodies impacts late-stage multiorgan metastasis
Advanced metastatic disease is difficult to manage and specific therapeutic targets are rare. We showed earlier that metastatic breast cancer cells use the activated conformer of adhesion receptor integrin αvβ...
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Article
Structural and kinetic determinants of protease substrates
Identifying physiological substrates of proteases still poses a challenge. An unbiased approach using the heterologous Escherichia coli proteome now identifies the structural and sequence determinants for caspase...
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Article
The Fas–FADD death domain complex structure unravels signalling by receptor clustering
The crystal structure of a complex between the cell surface receptor protein Fas and the Fas-associated death domain (FADD) protein - a central feature of the so-called death-inducing signalling complex of apo...
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Article
Proteolytic needles in the cellular haystack
The execution phase of cell death is driven by specific proteolytic signaling through cleavage of proteins by caspases. Within the mix of hundreds of newly identified caspase substrates lie the crucial proteol...
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Protocol
Apoptotic Caspase Activation and Activity
Caspases are central to the execution of apoptosis. Their proteolytic activity is responsible for the demise of cells in many physiological and pathological states. Great advances in understanding caspases hav...
