Equine herpesvirus-2 E10 gene product, but not its cellular homologue, activates NF-kappaB transcription factor and c-Jun N-terminal kinase.
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.
Thome
M
M
Institute of Biochemistry, University of Lausanne, Switzerland.
Martinon
F
F
Hofmann
K
K
Rubio
V
V
Steiner
V
V
Schneider
P
P
Mattmann
C
C
Tschopp
J
J
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D000074018:B-Cell CLL-Lymphoma 10 Protein; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D019169:Jurkat Cells; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; C488088:Bcl10 protein, mouse; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; C506387:Cflar protein, mouse; C118586:E10 protein, Equid herpesvirus 2; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D018124:Receptors, Tumor Necrosis Factor; D014764:Viral Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases