TRAF7 potentiates MEKK3-induced AP1 and CHOP activation and induces apoptosis.
The tumor necrosis factor receptor-associated factor (TRAF) protein family members are critically involved in activation of NF-kappaB, JNK, and p38 activation triggered by tumor necrosis factor (TNF) receptor family members and toll/interleukin-1 receptor (TIR)-containing receptors. TRAF proteins (except for TRAF1) contain an N-terminal RING finger domain that is essential for ... their functions. In this report, we identified a protein designated as TRAF7, which contains a RING finger domain and a zinc finger domain that are mostly conserved with those of TRAFs. TRAF7 also contains seven WD40 repeats at its C terminus. TRAF7 specifically interacted with MEKK3 and potentiated MEKK3-mediated AP1 and CHOP activation. Depletion of TRAF7 by antisense RNA inhibited MEKK3-mediated AP1 and CHOP activation. Moreover, overexpression of TRAF7 induced caspase-dependent apoptosis. Domain mapping experiments indicated that TRAF7 potentiated MEKK3-mediated AP1 and CHOP activation and induced apoptosis through distinct domains. Our studies identified a novel TRAF family member that is involved in MEKK3 signaling and apoptosis.
Mesh Terms:
Amino Acid Sequence, Apoptosis, Blotting, Northern, Blotting, Western, CCAAT-Enhancer-Binding Proteins, Carrier Proteins, Caspases, Cell Death, DNA Fragmentation, Genes, Reporter, Humans, Luciferases, MAP Kinase Kinase Kinase 3, MAP Kinase Kinase Kinases, Mitogen-Activated Protein Kinases, Models, Genetic, Molecular Sequence Data, Plasmids, Precipitin Tests, Protein Structure, Tertiary, Receptors, Tumor Necrosis Factor, Sequence Homology, Amino Acid, Tissue Distribution, Transcription Factor AP-1, Transcription Factor CHOP, Transcription Factors, Transfection, Tumor Necrosis Factor Receptor-Associated Peptides and Proteins, Zinc Fingers, p38 Mitogen-Activated Protein Kinases
Amino Acid Sequence, Apoptosis, Blotting, Northern, Blotting, Western, CCAAT-Enhancer-Binding Proteins, Carrier Proteins, Caspases, Cell Death, DNA Fragmentation, Genes, Reporter, Humans, Luciferases, MAP Kinase Kinase Kinase 3, MAP Kinase Kinase Kinases, Mitogen-Activated Protein Kinases, Models, Genetic, Molecular Sequence Data, Plasmids, Precipitin Tests, Protein Structure, Tertiary, Receptors, Tumor Necrosis Factor, Sequence Homology, Amino Acid, Tissue Distribution, Transcription Factor AP-1, Transcription Factor CHOP, Transcription Factors, Transfection, Tumor Necrosis Factor Receptor-Associated Peptides and Proteins, Zinc Fingers, p38 Mitogen-Activated Protein Kinases
J. Biol. Chem.
Date: Apr. 23, 2004
PubMed ID: 15001576
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