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Your search keyword '"Silke, John"' showing total 15 results
Start Over Author "Silke, John" Journal journal of biological chemistry
15 results on '"Silke, John"'

1. Tumor necrosis factor (TNF) signaling, but not TWEAK (TNF-like weak inducer of apoptosis)-triggered cIAP1 (cellular inhibitor of apoptosis protein 1) degradation, requires cIAP1 RING dimerization and E2 binding.

Author

Feltham, Rebecca L., primary, Moulin, Maryline, additional, Vince, James E., additional, Mace, Peter D., additional, Wong, Wendy Wei-Lynn, additional, Anderton, Holly, additional, Day, Catherine L., additional, Vaux, David L., additional, and Silke, John, additional

Published
2017
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2. In TNF-stimulated cells, RIPK1 promotes cell survival by stabilizing TRAF2 and cIAP1, which limits induction of non-canonical NF-κB and activation of caspase-8.

Author

Gentle, Ian E., primary, Wong, W. Wei-Lynn, additional, Evans, Joseph M., additional, Bankovacki, Alexandra, additional, Cook, Wendy D., additional, Khan, Nufail R., additional, Nachbur, Ulrich, additional, Rickard, James, additional, Anderton, Holly, additional, Moulin, Maryline, additional, Lluis, Josep Maria, additional, Moujalled, Donia M., additional, Silke, John, additional, and Vaux, David L., additional

Published
2016
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5. In TNF-stimulated Cells, RIPK1 Promotes Cell Survival by Stabilizing TRAF2 and cIAP1, which Limits Induction of Non-canonical NF-κB and Activation of Caspase-8

Author

Gentle, Ian E., primary, Wong, W. Wei-Lynn, additional, Evans, Joseph M., additional, Bankovacki, Alexandra, additional, Cook, Wendy D., additional, Khan, Nufail R., additional, Nachbur, Ulrich, additional, Rickard, James, additional, Anderton, Holly, additional, Moulin, Maryline, additional, Lluis, Josep Maria, additional, Moujalled, Donia M., additional, Silke, John, additional, and Vaux, David L., additional

Published
2011
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6. Tumor Necrosis Factor (TNF) Signaling, but Not TWEAK (TNF-like Weak Inducer of Apoptosis)-triggered cIAP1 (Cellular Inhibitor of Apoptosis Protein 1) Degradation, Requires cIAP1 RING Dimerization and E2 Binding

Author

Feltham, Rebecca, primary, Moulin, Maryline, additional, Vince, James E., additional, Mace, Peter D., additional, Wong, Wendy Wei-Lynn, additional, Anderton, Holly, additional, Day, Catherine L., additional, Vaux, David L., additional, and Silke, John, additional

Published
2010
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7. TRAF2 Must Bind to Cellular Inhibitors of Apoptosis for Tumor Necrosis Factor (TNF) to Efficiently Activate NF-κB and to Prevent TNF-induced Apoptosis

Author

Vince, James E., primary, Pantaki, Delara, additional, Feltham, Rebecca, additional, Mace, Peter D., additional, Cordier, Stephanie M., additional, Schmukle, Anna C., additional, Davidson, Angelina J., additional, Callus, Bernard A., additional, Wong, Wendy Wei-Lynn, additional, Gentle, Ian E., additional, Carter, Holly, additional, Lee, Erinna F., additional, Walczak, Henning, additional, Day, Catherine L., additional, Vaux, David L., additional, and Silke, John, additional

Published
2009
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12. HtrA2 Promotes Cell Death through Its Serine Protease Activity and Its Ability to Antagonize Inhibitor of Apoptosis Proteins

Author

Verhagen, Anne M., primary, Silke, John, additional, Ekert, Paul G., additional, Pakusch, Miha, additional, Kaufmann, Hitto, additional, Connolly, Lisa M., additional, Day, Catherine L., additional, Tikoo, Anjali, additional, Burke, Richard, additional, Wrobel, Carolyn, additional, Moritz, Robert L., additional, Simpson, Richard J., additional, and Vaux, David L., additional

Published
2002
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13. Tumor necrosis factor (TNF) signaling, but not TWEAK (TNF-like weak inducer of apoptosis)-triggered cIAP1 (cellular inhibitor of apoptosis protein 1) degradation, requires cIAP1 RING dimerization and E2 binding

Author

Catherine L. Day, W. Wei-Lynn Wong, James E Vince, Peter D. Mace, John Silke, Holly Anderton, David L. Vaux, Rebecca Feltham, Maryline Moulin, University of Zurich, and Silke, John

Subjects
Models, Molecular, TRAF2, Programmed cell death, 1303 Biochemistry, Molecular Conformation, Apoptosis, 610 Medicine & health, Inhibitor of apoptosis, 10263 Institute of Experimental Immunology, Biochemistry, Inhibitor of Apoptosis Proteins, 1307 Cell Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, Ubiquitin, Protein Interaction Mapping, 1312 Molecular Biology, Animals, Humans, Point Mutation, Molecular Biology, Cytokine TWEAK, 030304 developmental biology, 0303 health sciences, biology, Tumor Necrosis Factor-alpha, NF-kappa B, Cell Biology, Ubiquitin ligase, Cell biology, 030220 oncology & carcinogenesis, Tumor Necrosis Factors, biology.protein, 570 Life sciences, Tumor necrosis factor alpha, Additions and Corrections, Signal transduction, Dimerization, Protein Binding, Signal Transduction
Abstract

Cellular inhibitor of apoptosis (cIAP) proteins, cIAP1 and cIAP2, are important regulators of tumor necrosis factor (TNF) superfamily (SF) signaling and are amplified in a number of tumor types. They are targeted by IAP antagonist compounds that are undergoing clinical trials. IAP antagonist compounds trigger cIAP autoubiquitylation and degradation. The TNFSF member TWEAK induces lysosomal degradation of TRAF2 and cIAPs, leading to elevated NIK levels and activation of non-canonical NF-kappaB. To investigate the role of the ubiquitin ligase RING domain of cIAP1 in these pathways, we used cIAP-deleted cells reconstituted with cIAP1 point mutants designed to interfere with the ability of the RING to dimerize or to interact with E2 enzymes. We show that RING dimerization and E2 binding are required for IAP antagonists to induce cIAP1 degradation and protect cells from TNF-induced cell death. The RING functions of cIAP1 are required for full TNF-induced activation of NF-kappaB, however, delayed activation of NF-kappaB still occurs in cIAP1 and -2 double knock-out cells. The RING functions of cIAP1 are also required to prevent constitutive activation of non-canonical NF-kappaB by targeting NIK for proteasomal degradation. However, in cIAP double knock-out cells TWEAK was still able to increase NIK levels demonstrating that NIK can be regulated by cIAP-independent pathways. Finally we show that, unlike IAP antagonists, TWEAK was able to induce degradation of cIAP1 RING mutants. These results emphasize the critical importance of the RING of cIAP1 in many signaling scenarios, but also demonstrate that in some pathways RING functions are not required.

Published
2017

14. In TNF-stimulated cells, RIPK1 promotes cell survival by stabilizing TRAF2 and cIAP1, which limits induction of non-canonical NF-kappaB and activation of caspase-8.

Author

Gentle IE, Wong WW, Evans JM, Bankovacki A, Cook WD, Khan NR, Nachbur U, Rickard J, Anderton H, Moulin M, Lluis JM, Moujalled DM, Silke J, and Vaux DL

Subjects
Animals, Caspase 8 genetics, Cell Death drug effects, Cell Death physiology, Cell Survival drug effects, Cell Survival physiology, Cycloheximide pharmacology, Enzyme Activation drug effects, Enzyme Activation physiology, Inhibitor of Apoptosis Proteins genetics, Mice, Mice, Knockout, NF-kappa B genetics, Proteasome Endopeptidase Complex genetics, Proteasome Endopeptidase Complex metabolism, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases metabolism, Protein Stability, Protein Synthesis Inhibitors pharmacology, Receptor-Interacting Protein Serine-Threonine Kinases genetics, TNF Receptor-Associated Factor 2 genetics, Tumor Necrosis Factor-alpha pharmacology, NF-kappaB-Inducing Kinase, Caspase 8 metabolism, Inhibitor of Apoptosis Proteins metabolism, NF-kappa B metabolism, Receptor-Interacting Protein Serine-Threonine Kinases metabolism, TNF Receptor-Associated Factor 2 metabolism, Tumor Necrosis Factor-alpha metabolism
Abstract

RIPK1 is involved in signaling from TNF and TLR family receptors. After receptor ligation, RIPK1 not only modulates activation of both canonical and NIK-dependent NF-κB, but also regulates caspase-8 activation and cell death. Although overexpression of RIPK1 can cause caspase-8-dependent cell death, when RIPK1(-/-) cells are exposed to TNF and low doses of cycloheximide, they die more readily than wild-type cells, indicating RIPK1 has pro-survival as well as pro-apoptotic activities. To determine how RIPK1 promotes cell survival, we compared wild-type and RIPK1(-/-) cells treated with TNF. Although TRAF2 levels remained constant in TNF-treated wild-type cells, TNF stimulation of RIPK1(-/-) cells caused TRAF2 and cIAP1 to be rapidly degraded by the proteasome, which led to an increase in NIK levels. This resulted in processing of p100 NF-κB2 to p52, a decrease in levels of cFLIP(L), and activation of caspase-8, culminating in cell death. Therefore, the pro-survival effect of RIPK1 is mediated by stabilization of TRAF2 and cIAP1.

Published
2011
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15. TRAF2 must bind to cellular inhibitors of apoptosis for tumor necrosis factor (tnf) to efficiently activate nf-{kappa}b and to prevent tnf-induced apoptosis.

Author

Vince JE, Pantaki D, Feltham R, Mace PD, Cordier SM, Schmukle AC, Davidson AJ, Callus BA, Wong WW, Gentle IE, Carter H, Lee EF, Walczak H, Day CL, Vaux DL, and Silke J

Subjects
Amino Acid Motifs physiology, Animals, Cell Line, Inhibitor of Apoptosis Proteins genetics, Mice, Mice, Knockout, NF-kappa B genetics, Protein Binding physiology, Protein Structure, Tertiary physiology, Receptors, Tumor Necrosis Factor, Type I genetics, TNF Receptor-Associated Factor 2 genetics, Apoptosis physiology, Inhibitor of Apoptosis Proteins metabolism, NF-kappa B metabolism, Receptors, Tumor Necrosis Factor, Type I metabolism, TNF Receptor-Associated Factor 2 metabolism, Tumor Necrosis Factors metabolism
Abstract

Tumor necrosis factor (TNF) receptor-associated factor-2 (TRAF2) binds to cIAP1 and cIAP2 (cIAP1/2) and recruits them to the cytoplasmic domain of several members of the TNF receptor (TNFR) superfamily, including the TNF-TNFR1 ligand-receptor complex. Here, we define a cIAP1/2-interacting motif (CIM) within the TRAF-N domain of TRAF2, and we use TRAF2 CIM mutants to determine the role of TRAF2 and cIAP1/2 individually, and the TRAF2-cIAP1/2 interaction, in TNFR1-dependent signaling. We show that both the TRAF2 RING domain and the TRAF2 CIM are required to regulate NF-kappaB-inducing kinase stability and suppress constitutive noncanonical NF-kappaB activation. Conversely, following TNFR1 stimulation, cells bearing a CIM-mutated TRAF2 showed reduced canonical NF-kappaB activation and TNF-induced RIPK1 ubiquitylation. Remarkably, the RING domain of TRAF2 was dispensable for these functions. However, like the TRAF2 CIM, the RING domain of TRAF2 was required for protection against TNF-induced apoptosis. These results show that TRAF2 has anti-apoptotic signaling roles in addition to promoting NF-kappaB signaling and that efficient activation of NF-kappaB by TNFR1 requires the recruitment of cIAP1/2 by TRAF2.

Published
2009
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