Non-caspase proteases: triggers or amplifiers of apoptosis?

Schrader, Karen; Huai, Jisen; Jöckel, Lars; Oberle, Carolin; Borner, Christoph

doi:10.1007/s00018-010-0287-9

Cited by 38 publications

(26 citation statements)

References 139 publications

(186 reference statements)

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“…When LMP is triggered indirectly, it may serve as an amplification loop to strengthen apoptotic signaling (Schrader et al 2010;Repnik et al 2012). Although recent evidence suggests that LMPalso has an amplifying role in the death receptor pathway, there is still much controversy about its role, especially in tumor necrosis factor (TNF)-a and TNF-related apoptosis-inducing ligand (TRAIL) pathways (Hafner Č esen et al 2012).…”

Section: Lysosomes In Apoptosismentioning

confidence: 99%

The Endolysosomal System in Cell Death and Survival

Repnik

Česen

Turk

2013

Cold Spring Harbor Perspectives in Biology

117

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The endocytic pathway is a system specialized for the uptake of compounds from the cell microenvironment for their degradation. It contains an arsenal of hydrolases, including proteases, which are normally enclosed in membrane-bound organelles, but if released to the cytosol can initiate apoptosis signaling pathways. Endogenous and exogenous compounds have been identified that can mediate destabilization of lysosomal membranes, and it was shown that lysosomal proteases are not only able to initiate apoptotic signaling but can also amplify the apoptotic pathways initiated in other cellular compartments. The endocytic pathway also receives cargo destined for degradation via the autophagic pathway. By recycling energy and biosynthetic substrates, and by degrading damaged organelles and molecules, the endocytic system assists the autophagic system in resisting apoptotic stimuli. Steps leading to lysosomal membrane permeabilization and subsequent triggering of cell death as well as the therapeutic potential of intervention in lysosomal membrane permeabilization will be discussed.

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Section: Lysosomes In Apoptosismentioning

confidence: 99%

The Endolysosomal System in Cell Death and Survival

Repnik

Česen

Turk

2013

Cold Spring Harbor Perspectives in Biology

117

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“…the key activation step for lysosome function in apoptosis is represented by the destabilization of lysosomal membranes (also referred as lysosomal membrane permeabilization, LMP) to allow the release of lysosomal content into the cytosol [17]. Then, proteases cleave apoptotic players, such as Bcl-2 family members, possibly regulating also mitochondrial function [18,19]. …”

Section: Lysosomesmentioning

confidence: 99%

Morphological Features of Organelles during Apoptosis: An Overview

Bottone

Santin

Aredia

et al. 2013

Cells

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An apoptotic program leading to controlled cell dismantling implies perturbations of nuclear dynamics, as well as changes affecting the organelle structure and distribution. In human cancer cells driven to apoptosis by different stimuli, we have recently investigated the morphological properties of several organelles, including mitochondria, lysosomes, endoplasmic reticulum and Golgi apparatus. In this review, we will discuss the body of evidence in the literature suggesting that organelles are generally relocated and/or degraded during apoptosis, irrespectively of the apoptogenic stimulus and cell type.

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“…However, our data indicate that murine MyD88 is also diminished in Yersinia-induced apoptosis (data not shown). Alternative proteases other than caspases activated during apoptosis, such as serine proteases or cathepsins, could be responsible for the processing of mouse MyD88 (46). The removal of MyD88 in apoptosis execution may consequently fulfill a particular, conserved function.…”

Section: Discussionmentioning

confidence: 99%

Cell Death Triggered by Yersinia enterocolitica Identifies Processing of the Proinflammatory Signal Adapter MyD88 as a General Event in the Execution of Apoptosis

Novikova

Czymmeck

Deuretzbacher

et al. 2014

The Journal of Immunology

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Many pathogenic microorganisms have evolved tactics to modulate host cell death or survival pathways for establishing infection. The enteropathogenic bacterium Yersinia enterocolitica deactivates TLR-induced signaling pathways, which triggers apoptosis in macrophages. In this article, we show that Yersinia-induced apoptosis of human macrophages involves caspase-dependent cleavage of the TLR adapter protein MyD88. MyD88 was also cleaved when apoptosis was mediated by overexpression of the Toll–IL-1R domain–containing adapter inducing IFN-β in epithelial cells. The caspase-processing site was mapped to aspartate-135 in the central region of MyD88. MyD88 is consequently split by caspases in two fragments, one harboring the death domain and the other the Toll–IL-1R domain. Caspase-3 was identified as the protease that conferred the cleavage of MyD88 in in vitro caspase assays. In line with a broad role of caspase-3 in the execution of apoptosis, the processing of MyD88 was not restricted to Yersinia infection and to proapoptotic Toll–IL-1R domain–containing adapter inducing IFN-β signaling, but was also triggered by staurosporine treatment. The cleavage of MyD88 therefore seems to be a common event in the advanced stages of apoptosis, when caspase-3 is active. We propose that the processing of MyD88 disrupts its scaffolding function and uncouples the activation of TLR and IL-1Rs from the initiation of proinflammatory signaling events. The disruption of MyD88 may consequently render dying cells less sensitive to proinflammatory stimuli in the execution phase of apoptosis. The cleavage of MyD88 could therefore be a means of conferring immunogenic tolerance to apoptotic cells to ensure silent, noninflammatory cell demise.

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Non-caspase proteases: triggers or amplifiers of apoptosis?

Cited by 38 publications

References 139 publications

The Endolysosomal System in Cell Death and Survival

The Endolysosomal System in Cell Death and Survival

Morphological Features of Organelles during Apoptosis: An Overview

Cell Death Triggered by Yersinia enterocolitica Identifies Processing of the Proinflammatory Signal Adapter MyD88 as a General Event in the Execution of Apoptosis

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