Human Caspase-7 Activity and Regulation by Its N-terminal Peptide

Denault, Jean‐Bernard; Salvesen, Guy S.

doi:10.1074/jbc.m305110200

Cited by 99 publications

(113 citation statements)

References 40 publications

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“…At first glance our data also point to caspase-3, and not caspase-7, as the primary executioner. There are several observations that support this idea: (i) caspase-3 activity is required for caspase-7 activation [50] and (ii) the generally higher concentrations of caspase-3 than caspase-7 in vivo. Although the last is not well defined, it has been shown, at least for the 293 human embryonic kidney cells, that intracellular caspase-3 concentration can be as high as 100-200 nM [51] and that of caspase-7 around 65 nM (H. Stennicke and G. Salvesen, personal communication).…”

Section: Discussionmentioning

confidence: 97%

Cleavage of MAGI-1, a tight junction PDZ protein, by caspases is an important step for cell-cell detachment in apoptosis

et al. 2006

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MAGI-1, a member of the MAGUK family of proteins, is shown to be rapidly cleaved during Fasinduced apoptosis in mouse 3T3 A31 cells, and in UV irradiation-and staurosporine-induced apoptosis in HaCaT cells. This generates a 97 kDa N-terminal fragment that dissociates from the cell membrane; a process that is largely prevented in the presence of the caspase inhibitor Z-VADfmk. In addition, we show that in vitro translated radiolabelled MAGI-1 is efficiently cleaved into 97 kDa and 68 kDa fragments by caspases-3 and -7 at physiological concentrations and mutating the MAGI-1 Asp 761 to Ala completely abolished the caspase-induced cleavage. was delayed during apoptosis, whereas other caspase-dependent processes such as nuclear condensation were not affected, suggesting that cell detachment is parallel to them. Thus, MAGI-1 cleavage appears to be an important step in the disassembly of cell-cell contacts during apoptosis.

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Section: Discussionmentioning

confidence: 97%

Cleavage of MAGI-1, a tight junction PDZ protein, by caspases is an important step for cell-cell detachment in apoptosis

et al. 2006

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“…Removal of the prodomain of caspase-7 is required for its efficient activation in vivo, possibly because the highly charged N-terminal prodomain results in the physical sequestration of caspase-7 from its upstream caspase. 39 To our knowledge there has only been one earlier study to investigate the importance of the removal of prodomain of caspase-6 in cells. 40 They showed that the removal of the prodomain of caspase-6 was required both for caspase-8 processing and also for serum-depletion-mediated apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Ordering of caspases in cells undergoing apoptosis by the intrinsic pathway

et al. 2009

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Caspases are a family of aspartate-specific cysteine proteases responsible for the biochemical and morphological changes that occur during the execution phase of apoptosis. The hierarchical ordering of caspases has been clearly established using dATPactivated cell lysates to model the intrinsic pathway induced by initial mitochondrial perturbation. In this model, caspase-9, the apical caspase, directly processes and activates the effector caspases, caspase-3 and -7, and then active caspase-3 but not caspase-7, processes caspase-2 and -6, and subsequently the activated caspase-6 processes caspase-8 and -10. To address the possibility that this model in vitro system might not reflect the precise ordering of caspases in intact cells, we have examined this possibility in cells induced to undergo apoptosis by activation of the intrinsic pathway. We have used caspase deficient cells, small interference RNA for caspase-6 and -7, and a specific caspase-3 inhibitor. In contrast to the earlier in vitro studies, we now show that in intact cells caspase-7 can also directly process and activate caspase-2 and -6. The processing of caspase-2 and -6 occurs within the cytoplasm and active caspase-6 is then responsible for both the processing of caspase-8 and the cleavage of caspase-6 substrates, including lamin A/C. Apoptosis, a major form of cell death used to remove unwanted or excess cells, is characterized by a plethora of morphological and biochemical changes resulting primarily from the activation of a family of cysteine proteases, which cleave their substrates at specific aspartate residues. 1-4 Two major apoptotic pathways have been described, the intrinsic pathway involving initial mitochondrial perturbation resulting from cellular stress or cytotoxic insults and the extrinsic pathway, which is triggered by the activation of death receptors of the TNF family. 5-7 Caspase-8 and -9, the apical caspases in the extrinsic and intrinsic pathways, possess a protein interaction prodomain, which result in their recruitment and subsequent activation within cellular complexes, namely the death-inducing signaling complex (DISC) and the Apaf-1 apoptosome, respectively, and the subsequent activation of effector caspases, such as caspase-3, -6 and -7. 5,[8][9][10] Caspases are synthesized as single-chain zymogens, containing an N-terminal prodomain, as well as large (B20 kDa) and small (B10 kDa) subunits, with the basic catalytic domain forming from a large and small subunits. 1,3,4 Caspase-2 also has a sizeable prodomain, but it is unclear whether it should be considered an initiator or an effector caspase. 3 Although caspase-2 has been proposed to act upstream of mitochondria and to be activated within the PIDDosome, it may also be activated downstream of caspase-3. 11-14 Using recombinant proteins, caspase-3, -8 and to a lesser extent caspase-7 can process caspase-2. 15 The physiological role of caspase-2 is not known and no marked phenotype is observed in caspase-2 À/À mice. Caspase-6 is generally considered to be an effector casp...

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“…However, the inherent cleavage site specificity of caspases have been applied to make active site probes that show some degree of selectivity for individual caspases, 10 and when these are coupled with selective antisera the identity of active caspases in complex mixtures is more readily disclosed. [11][12][13][14] Specificity for protein substrates Exosites. Having a preferred cleavage site specificity is not sufficient for proteolysis of natural proteins; appropriate presentation of the cleavage site seems critical for efficient hydrolysis.…”

Section: What It Takes To Be a Caspasementioning

confidence: 99%

Caspase substrates

2006

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The relatively common occurrence of sequences within proteins that match the consensus substrate specificity of caspases in intracellular proteins suggests a multitude of substrates in vivo -somewhere in the order of several hundred in humans alone. Indeed, the list of proteins that are reported to be cleaved by caspases in vitro proliferates rapidly. However, only a few of these proteins have been rigorously established as biologically or pathologically relevant, bona fide substrates in vivo. Many of them probably simply represent 'innocent bystanders' or erroneous assignments. In this review we discuss concepts of caspase substrate recognition and specificity, give resources for the discovery and annotation of caspase substrates, and highlight some specific human or mouse proteins where there is strong evidence for biologic or pathologic relevance.

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Human Caspase-7 Activity and Regulation by Its N-terminal Peptide

Cited by 99 publications

References 40 publications

Cleavage of MAGI-1, a tight junction PDZ protein, by caspases is an important step for cell-cell detachment in apoptosis

Cleavage of MAGI-1, a tight junction PDZ protein, by caspases is an important step for cell-cell detachment in apoptosis

Ordering of caspases in cells undergoing apoptosis by the intrinsic pathway

Caspase substrates

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