IG20 (MADD splice variant-5), a proapoptotic protein, interacts with DR4/DR5 and enhances TRAIL-induced apoptosis by increasing recruitment of FADD and caspase-8 to the DISC
pmid: 15208670
IG20 (MADD splice variant-5), a proapoptotic protein, interacts with DR4/DR5 and enhances TRAIL-induced apoptosis by increasing recruitment of FADD and caspase-8 to the DISC
Recently, we identified Insulinoma-Glucagonoma clone 20 (IG20) that can render cells more susceptible to tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis. In addition, it can slow cell proliferation, and enhance drug- and radiation-induced cell death. TNF-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in some cancer cells and render others susceptible to cotreatment with drugs and irradiation, with little or no effect on most normal cells. In this study, we investigated the potential of IG20 to enhance TRAIL-induced apoptosis and found that it can render cells more susceptible to TRAIL treatment through enhanced activation of caspases. Further, we showed that this effect can be suppressed by caspase inhibitors, p35 and CrmA, and a dominant-negative Fas-associated death domain-containing protein (DN-FADD). Results from colocalization and immunoprecipitation studies showed that IG20 can interact with TRAIL death receptors (DR), DR4 and DR5 and increase recruitment of FADD and caspase-8 into the TRAIL death-inducing signaling complex (DISC). These results indicate that IG20 is a novel protein that can enhance TRAIL-induced apoptosis by facilitating DISC formation.
- University of Illinois at Chicago United States
- University of Chicago United States
Caspase 8, Death Domain Receptor Signaling Adaptor Proteins, Membrane Glycoproteins, Fas-Associated Death Domain Protein, Apoptosis, Cysteine Proteinase Inhibitors, Caspase Inhibitors, Receptors, Tumor Necrosis Factor, TNF-Related Apoptosis-Inducing Ligand, Protein Transport, Receptors, TNF-Related Apoptosis-Inducing Ligand, Receptors, Tumor Necrosis Factor, Type I, Caspases, Multiprotein Complexes, Mutation, Guanine Nucleotide Exchange Factors, Humans, Apoptosis Regulatory Proteins, Adaptor Proteins, Signal Transducing, HeLa Cells
Caspase 8, Death Domain Receptor Signaling Adaptor Proteins, Membrane Glycoproteins, Fas-Associated Death Domain Protein, Apoptosis, Cysteine Proteinase Inhibitors, Caspase Inhibitors, Receptors, Tumor Necrosis Factor, TNF-Related Apoptosis-Inducing Ligand, Protein Transport, Receptors, TNF-Related Apoptosis-Inducing Ligand, Receptors, Tumor Necrosis Factor, Type I, Caspases, Multiprotein Complexes, Mutation, Guanine Nucleotide Exchange Factors, Humans, Apoptosis Regulatory Proteins, Adaptor Proteins, Signal Transducing, HeLa Cells
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