TRADD is critical for resistance to TRAIL-induced cell death through NF-κB activation
Copyright policy )TRADD is critical for resistance to TRAIL-induced cell death through NF-κB activation
One major obstacle in the clinical application of TRAIL as a cancer therapeutic agent is the acquisition of TRAIL resistance. We found that deficiency of TRADD sensitizes cells to TRAIL-induced apoptosis. Enhanced cell death in TRADD(-/-) MEFs is associated with defective NF-κB activation, indicating that the pro-survival function of TRADD in TRAIL signaling is mediated at least in part via NF-κB activation. Moreover, siRNA knock-down of TRADD in cancer cells sensitizes them to TRAIL-induced apoptosis. Thus, TRADD has a survival role in TRAIL signaling and may be one potential target for overcoming TRAIL resistance in cancer therapy.
- Yonsei University Medical Library Korea (Republic of)
- Myongji University Korea (Republic of)
- Yonsei University Health System Korea (Republic of)
- Ajou University Korea (Republic of)
Poly (ADP-Ribose) Polymerase-1, TRAIL, Apoptosis, NF-κB, TNF-Related Apoptosis-Inducing Ligand, Mice, Extracellular Signal-Regulated MAP Kinases/metabolism, Fibroblasts/physiology, RNA, Small Interfering, Extracellular Signal-Regulated MAP Kinases, Cells, Cultured, Poly(ADP-ribose) Polymerases/metabolism, Mice, Knockout, Caspase 8, Tumor, Cultured, Caspase 3, TNF-Related Apoptosis-Inducing Ligand/genetics, NF-kappa B, TNF Receptor-Associated Death Domain Protein/genetics, NF-kappa B/metabolism*, TNF Receptor-Associated Death Domain Protein, Small Interfering/genetics, Poly(ADP-ribose) Polymerases, Caspase 3/metabolism, Signal Transduction, Cell death, 570, Small Interfering/metabolism, Cells, Knockout, Cell Line, Caspase 8/metabolism, Cell Line, Tumor, Animals, Humans, JNK Mitogen-Activated Protein Kinases/metabolism, TNF Receptor-Associated Death Domain Protein/metabolism*, Signal Transduction/physiology, JNK Mitogen-Activated Protein Kinases, Fibroblasts, TRADD, Apoptosis/physiology*, TNF-Related Apoptosis-Inducing Ligand/metabolism*, Enzyme Activation, Fibroblasts/cytology, RNA
Poly (ADP-Ribose) Polymerase-1, TRAIL, Apoptosis, NF-κB, TNF-Related Apoptosis-Inducing Ligand, Mice, Extracellular Signal-Regulated MAP Kinases/metabolism, Fibroblasts/physiology, RNA, Small Interfering, Extracellular Signal-Regulated MAP Kinases, Cells, Cultured, Poly(ADP-ribose) Polymerases/metabolism, Mice, Knockout, Caspase 8, Tumor, Cultured, Caspase 3, TNF-Related Apoptosis-Inducing Ligand/genetics, NF-kappa B, TNF Receptor-Associated Death Domain Protein/genetics, NF-kappa B/metabolism*, TNF Receptor-Associated Death Domain Protein, Small Interfering/genetics, Poly(ADP-ribose) Polymerases, Caspase 3/metabolism, Signal Transduction, Cell death, 570, Small Interfering/metabolism, Cells, Knockout, Cell Line, Caspase 8/metabolism, Cell Line, Tumor, Animals, Humans, JNK Mitogen-Activated Protein Kinases/metabolism, TNF Receptor-Associated Death Domain Protein/metabolism*, Signal Transduction/physiology, JNK Mitogen-Activated Protein Kinases, Fibroblasts, TRADD, Apoptosis/physiology*, TNF-Related Apoptosis-Inducing Ligand/metabolism*, Enzyme Activation, Fibroblasts/cytology, RNA
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