The ‘complexities’ of life and death: Death receptor signalling platforms

Dickens, Laura S.; Powley, Ian; Hughes, Michelle A.; MacFarlane, Marion

doi:10.1016/j.yexcr.2012.04.005

Cited by 177 publications

(135 citation statements)

References 71 publications

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“…Caspase-8, after autoprocessing, cleaves and activates caspase-3 and caspase-7, resulting in cell demise by apoptosis. Caspase-8 also cleaves and activates the BH3-only protein Bid, thereby activating the mitochondrial apoptosis pathway (Dickens et al, 2012 Snail, a transcription factor involved in epithelial-mesenchymal transition (EMT) is also marked for degradation by SCF b-TRCP upon phosphorylation by GSK-3 (Zhou et al, 2004). Indeed, we and others observed a similar mechanism by which Mcl-1 is destabilized upon phosphorylation by GSK-3 (Ding et al, 2007;Inuzuka et al, 2011;Maurer et al, 2006;Morel et al, 2009;Zhao et al, 2007).…”

Section: Box 2 Intrinsic and Extrinsic Apoptosis Pathwaysmentioning

confidence: 51%

“…cIAP proteins are E3 ubiquitin ligases that promote survival through K63-linked ubiquitylation of constituents of TNFR complex I, such as RIPK1 (Gyrd-Hansen and Meier, 2010). c-FLIP, a close relative of caspase-8 without enzymatic activity, prevents proapoptotic homodimeric activation of caspase-8 by heterodimerizing with caspase-8 (Dickens et al, 2012). In the absence of these proteins, the activation of TNFR1 by TNF turns into a cell death signal, through the assembly of the TNFR complex II, which is a protein platform activating caspase-8 and thereby apoptosis.…”

Section: Gsk-3 As a Mediator Of Cell Survivalmentioning

confidence: 99%

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GSK-3 – at the crossroads of cell death and survival

Maurer

Preiss

Brauns-Schubert

et al. 2014

Journal of Cell Science

152

130

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Glycogen synthase kinase 3 (GSK-3) is involved in various signaling pathways controlling metabolism, differentiation and immunity, as well as cell death and survival. GSK-3 targets transcription factors, regulates the activity of metabolic and signaling enzymes, and controls the half-life of proteins by earmarking them for degradation. GSK-3 is unique in its mode of substrate recognition and the regulation of its kinase activity, which is repressed by pro-survival phosphoinositide 3-kinase (PI3K)-AKT signaling. In turn, GSK-3 exhibits pro-apoptotic functions when the PI3K-AKT pathway is inactive. Nevertheless, as GSK-3 is crucially involved in many signaling pathways, its role in cell death regulation is not uniform, and in some situations it promotes cell survival. In this Commentary, we focus on the various aspects of GSK-3 in the regulation of cell death and survival. We discuss the effects of GSK-3 on the regulation of proteins of the BCL-2 family, through which GSK-3 exhibits pro-apoptotic activity. We also highlight the prosurvival activities of GSK-3, which are observed in the context of nuclear factor kB (NFkB) signaling, and we discuss how GSK-3, by impacting on cell death and survival, might play a role in diseases such as cancer.

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Section: Box 2 Intrinsic and Extrinsic Apoptosis Pathwaysmentioning

confidence: 51%

Section: Gsk-3 As a Mediator Of Cell Survivalmentioning

confidence: 99%

GSK-3 – at the crossroads of cell death and survival

Maurer

Preiss

Brauns-Schubert

et al. 2014

Journal of Cell Science

152

130

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“…C-FLIP is believed to regulate apoptosis by inhibiting caspase-8 activation (25). We then examined the effects of caspase-8-specific inhibitor Z-IETD on PS1-induced apoptosis.…”

Section: Ps1-induced Apoptosis Was Partially Blocked By Inhibition Ofmentioning

confidence: 99%

Cellular FLICE-like Inhibitory Protein (c-FLIP) and PS1-associated Protein (PSAP) Mediate Presenilin 1-induced γ-Secretase-dependent and -independent Apoptosis, Respectively

Zeng¹,

Zhang³

et al. 2015

Journal of Biological Chemistry

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Background: The PS1-induced apoptosis mechanism is not fully understood. Results: PS1-induced apoptosis depends on PSAP-Bax complex formation and ␥-catalyzed turnover of c-FLIP. Conclusion: PS1 induces apoptosis through the ␥-secretase-dependent PS1-c-FLIP-caspase-8-Bid cascade and ␥-secretaseindependent PS1-PSAP cascade, which converge on Bax to activate the mitochondrial apoptotic pathway. PS2 induced apoptosis through a different pathway. Significance: This study provides new insight into the mechanism of PS1-induced apoptosis.

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“…1). The extrinsic pathway starts when a proapoptotic ligand binds to one of the death receptors on the extracellular side (Dickens et al, 2012). The binding of the ligand leads to the formation of the death-inducible signaling complex on the intracellular side of the membrane which triggers activation of caspase-8 (Muzio et al, 1996;van Raam and Salvesen, 2012).…”

Section: Apoptosismentioning

confidence: 99%

The role of ion channels and intracellular metal ions in apoptosis of Xenopus oocytes

Englund¹

2014

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Apoptosis is one type of programmed cell death, important during tissue development and to maintain the tissue homeostasis. Apoptosis comprises a complex network of internal signaling pathways, and an important part of this signaling network is the action of voltage‐gated ion channels. The aim of this thesis was to explore the role of ion channels and the role of intracellular metal ions during apoptosis in Xenopus laevis oocytes. The reasons for using these oocytes are that they are large, robust, easy to handle, and easy to study electrophysiologically. Apoptosis was induced either chemically by incubation of the oocytes in staurosporine (STS) or mechanically by centrifugation of the oocytes. Ion currents were measured by a two‐electrode voltage clamp technique, intracellular ion concentrations were measured either directly by in‐house developed K+‐selective microelectrodes or indirectly by the electrophysiological technique, and apoptosis was measured by caspase‐3 activation. Paper I describes that the intracellular K+ concentration was reduced by about 30 % during STS‐induced apoptosis. However, this reduction was prevented by excessive expression of exogenous ion channels. Despite the magnitude of the intracellular K+ concentration, either normal or reduced level, the oocytes displayed normal signs of apoptosis, suggesting that the intracellular K+ reduction was not required for the apoptotic process. Because the intracellular K+ concentration was not critical for apoptosis we searched for other ion fluxes by exploring the electrophysiological properties of X. laevis oocytes. Paper II, describes a non‐inactivating Na+ current activated at positive membrane voltages that was upregulated by a factor of five during STS‐induced apoptosis. By preventing influx of Na+, the apoptotic signaling network involving capsase‐3 was prevented. To molecularly identify this voltage‐gated Na channel, the X. tropicalis genome and conserved regions of the human SCNA genes were used as a map. Paper III, shows that the voltage‐gated Na channel corresponds to the SCN2A gene ortholog and that supression of this SCN2A ortholog using miRNA prevented cell death. In conclusion, this thesis work demonstrated that a voltage‐gated Na channel is critical for the apoptotic process in X. laevis oocytes by increasing the intracellular Na+ concentration

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The ‘complexities’ of life and death: Death receptor signalling platforms

Cited by 177 publications

References 71 publications

GSK-3 – at the crossroads of cell death and survival

GSK-3 – at the crossroads of cell death and survival

Cellular FLICE-like Inhibitory Protein (c-FLIP) and PS1-associated Protein (PSAP) Mediate Presenilin 1-induced γ-Secretase-dependent and -independent Apoptosis, Respectively

The role of ion channels and intracellular metal ions in apoptosis of Xenopus oocytes

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