Reprieval from execution: the molecular basis of caspase inhibition

Stennicke, Henning R.; Ryan, Ciara; Salvesen, Guy S.

doi:10.1016/s0968-0004(01)02045-x

Cited by 159 publications

(117 citation statements)

References 58 publications

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“…None of these inhibitors increased the clonogenic survival of g-irradiated HCT116 WT, 14-3-3s À/À or Chk2 À/À cells ( Figure 8d-f). As the bioavailability and specificity of such chemical inhibitors are uncertain, we stably transfected HCT116 WT cells with a cDNA coding for the Baculovirus-derived p35 inhibitor of apoptosis protein, a proteaceous pancaspase inhibitor (Stennicke et al, 2002). Control experiments confirmed that p35 strongly inhibited apoptosis induced by cytotoxic agents such as staurosporin, cisplatin and camptothecin (Supplementary Figure 1).…”

Section: Resultsmentioning

confidence: 95%

“…Cells were grown in McCoy's 5a medium (Eurobio, Les Ulis, France) supplemented with 10% fetal bovine serum (ATGC, Cergy-Pontoise, France), 1% PS (Gibco, Worcester, USA), 1% L-glutamine (Eurobio), 1 mM sodium pyruvate (Gibco) and 10 mM N-2-hydroxyethylpiperazine-N 0 -2-ethanesulfonic acid (Sigma, Saint Louis, USA), in humidified atmosphere containing 5% CO 2 at 371C (Castedo et al, 2004b, c). To generate p35 clones, the HCT116 parental cells were transfected with a vector encoding p35 (Stennicke et al, 2002;Date et al, 2003), selected with geneticin (0.5 mg/ml, Invitrogen, Cergy-Pontoise, France) and subcloned by limiting dilution. As control, HCT116 parental cells clones were transfected with a pCMV vector (Sigma) that confers resistance to geneticin.…”

Section: Discussionmentioning

confidence: 99%

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Caspase independence of radio-induced cell death

et al. 2006

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Section: Resultsmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Caspase independence of radio-induced cell death

et al. 2006

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“…A group of cysteine-dependent aspartate-specific proteases, the caspases (Alnemri et al, 1996), carries out apoptosis by cleaving a broad range of cellular proteins, ultimately resulting in cell death (Shi, 2002). Initiator caspases (caspase-2, -8, -9, -10), activated by their own proximity-induced proteolysis, in turn activate the so-called executioner caspases (caspase-3, -6, -7) that ultimately carry out apoptotic destruction of target proteins and the cell itself (Stennicke et al, 2002). Members of both the Bcl-2 and the inhibitor of apoptosis (IAP) families are widely expressed in cancers (Tsujimoto et al, 1985;Weller et al, 1995;Ambrosini et al, 1997;Liston et al, 1997;LaCasse et al, 1998;Wagenknecht et al, 1999;Tamm et al, 2000), and increasing evidence indicates they afford protection to cancer cells by controlling caspase activation.…”

Section: Introductionmentioning

confidence: 99%

Loss of XIAP protein expression by RNAi and antisense approaches sensitizes cancer cells to functionally diverse chemotherapeutics

et al. 2004

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Stable expression of short-hairpin RNAs (shRNAs) directed against the X-linked inhibitor of apoptosis (XIAP) resulted in the generation of three MDA-MB-231 cell lines (XIAP shRNA cells) with reductions in XIAP mRNA and protein levels 485% relative to MDA-MB-231 cells stably transfected with the U6 RNA polymerase III promoter alone (U6 cells). This RNA interference (RNAi) approach dramatically sensitized these cells to killing by the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Importantly, loss of XIAP also sensitized the cells to killing by taxanes but had no additional effects on killing by carboplatin and doxorubicin. The increased sensitivity of the XIAP shRNA cells to killing by TRAIL and taxanes correlated with enhanced caspase cleavage and activation, including caspase-8, and robust processing of poly(ADP-ribose) polymerase and BID compared to U6 cells. Additionally, increasing XIAP levels by adenovirus-mediated expression protected both XIAP shRNA and U6 cells from TRAIL killing in a dose-dependent manner. The effects observed by stable RNAi with respect to TRAIL sensitization were also achieved following downregulation of XIAP in Panc-1 cells treated with a second-generation, mixed-backbone antisense oligonucleotide, AEG 35156/GEM640. These data indicate that reducing XIAP protein expression by either RNAi or antisense approaches increases cancer cell susceptibility to functionally diverse chemotherapeutic agents and supports the notion that downregulation of XIAP in vivo may synergize with disease-relevant chemotherapeutic regimes, including TRAIL and taxanes, to increase the effectiveness of antineoplastic agents.

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“…Viruses have elaborated multiple ways to evade the apoptotic response by inhibiting caspases (Stennicke et al, 2002), but the endogenous inhibitors found in humans are of two types. One of these, FLIP, prevents activation of the extrinsic pathway by blocking caspase 8 recruitment and activation (for review see Tschopp et al, 1998).…”

Section: Caspase Inhibitionmentioning

confidence: 99%

Caspases on the brain

Troy

Salvesen

2002

J of Neuroscience Research

106

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The basic mechanisms that underlie neurodegenerative diseases are unknown. Loss of function of specific regions of the brain is due to incapacitation of cells that constitute those regions. Cells can simply stop functioning normally (neurons may cease to transmit signals), or they may die. There is now evidence that the pathology of several neurodegenerative diseases is due to inappropriate apoptosis. This being the case, an understanding of the mediators of apoptosis, their identities, and their role in orchestrating death would be a vital step toward remedying the diseases. The central components of apoptotic pathways, proteases of the caspase family, are present in latent forms in all nucleated cells. Their activity is balanced by specific activation and inactivation events, and the molecular and biochemical controls have been well established in vitro and in model transformed cell lines. In this Mini‐Review, we consider the current status of the basic control mechanisms and how these may be subverted during neurodegeneration. © 2002 Wiley‐Liss, Inc.

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Reprieval from execution: the molecular basis of caspase inhibition

Cited by 159 publications

References 58 publications

Caspase independence of radio-induced cell death

Caspase independence of radio-induced cell death

Loss of XIAP protein expression by RNAi and antisense approaches sensitizes cancer cells to functionally diverse chemotherapeutics

Caspases on the brain

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