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Equine herpesvirus-2 E10 gene product, but not its cellular homologue, activates NF-kappaB transcription factor and c-Jun N-terminal kinase.
Journal of Biological Chemistry
We have previously reported on the death effector domain containing E8 gene product from equine herpesvirus-2, designated FLICE inhibitory protein (v-FLIP), and on its cellular homologue, c-FLIP, which inhibit the activation of caspase-8 by death receptors. Here we report on the structure and function of the E10 gene product of equine herpesvirus-2, designated v-CARMEN, and on its cellular homologue, c-CARMEN, which contain a caspase-recruiting domain (CARD) motif. c-CARMEN is highly homologous to the viral protein in its N-terminal CARD motif but differs in its C-terminal extension. v-CARMEN and c-CARMEN interact directly in a CARD-dependent manner yet reveal different binding specificities toward members of the tumor necrosis factor receptor-associated factor (TRAF) family. v-CARMEN binds to TRAF6 and weakly to TRAF3 and, upon overexpression, potently induces the c-Jun N-terminal kinase (JNK), p38, and nuclear factor (NF)-kappaB transcriptional pathways. c-CARMEN or truncated versions thereof do not appear to induce JNK and NF-kappaB activation by themselves, nor do they affect the JNK and NF-kappaB activating potential of v-CARMEN. Thus, in contrast to the cellular homologue, v-CARMEN may have additional properties in its unique C terminus that allow for an autonomous activator effect on NF-kappaB and JNK. Through activation of NF-kappaB, v-CARMEN may regulate the expression of the cellular and viral genes important for viral replication.
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Apoptosis, CASP8 and FADD-Like Apoptosis Regulating Protein, Calcium-Calmodulin-Dependent Protein Kinases/metabolism, Carrier Proteins/metabolism, Caspases/metabolism, Enzyme Activation, Humans, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, Jurkat Cells, Mice, Mitogen-Activated Protein Kinases, Molecular Sequence Data, NF-kappa B/metabolism, Neoplasm Proteins, Receptors, Tumor Necrosis Factor/metabolism, Sequence Homology, Amino Acid, Viral Proteins/metabolism, p38 Mitogen-Activated Protein Kinases
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