c-E10 is a caspase-recruiting domain-containing protein that interacts with components of death receptors signaling pathway and activates nuclear factor-kappaB.
Members of the tumor necrosis factor receptor superfamily induce apoptosis via interaction with FADD and regulate cell growth and differentiation through TRADD and TRAFs molecules. While screening for molecules involved in the regulation of death receptor signaling, we identified a novel protein, c-E10. c-E10 contains an amino-terminal caspase-recruiting domain (CARD) and shares a sequence homologous with E10, a viral CARD-containing protein that binds to c-E10. In transfection experiments c-E10 oligomerizes, binds to the cytoplasmic portion of TRAIL receptor 1 (DR4) and coprecipitates with TRADD. Expression of c-E10 under the control of a doxycycline-dependent transcriptional transactivator results in NF-kappaB activation, which is inhibited by dominant negative forms of TRAF2 and NIK kinase. Thus, our results suggest that c-E10 is an adapter protein that activates NF-kappaB through a molecular pathway involved in death receptor signaling.
Fondazione A. Cesalpino, I Clinica Medica, V.le Policlinico 155, 00161 Roma, Italy.
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D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000074018:B-Cell CLL-Lymphoma 10 Protein; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D002352:Carrier Proteins; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins