Abstract
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
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Amino Acid Sequence
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Apoptosis*
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Blotting, Northern
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Blotting, Western
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CCAAT-Enhancer-Binding Proteins / physiology*
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Carrier Proteins / chemistry
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Carrier Proteins / physiology*
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Caspases / metabolism
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Cell Death
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DNA Fragmentation
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Genes, Reporter
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Humans
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Luciferases / metabolism
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MAP Kinase Kinase Kinase 3
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MAP Kinase Kinase Kinases / chemistry*
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Mitogen-Activated Protein Kinases / metabolism
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Models, Genetic
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Molecular Sequence Data
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Plasmids / metabolism
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Precipitin Tests
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Protein Structure, Tertiary
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Receptors, Tumor Necrosis Factor / chemistry*
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Sequence Homology, Amino Acid
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Tissue Distribution
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Transcription Factor AP-1 / physiology*
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Transcription Factor CHOP
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Transcription Factors / physiology*
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Transfection
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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins*
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Zinc Fingers
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p38 Mitogen-Activated Protein Kinases
Substances
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CCAAT-Enhancer-Binding Proteins
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Carrier Proteins
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DDIT3 protein, human
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Receptors, Tumor Necrosis Factor
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TRAF7 protein, human
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Traf7 protein, mouse
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Transcription Factor AP-1
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Transcription Factors
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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
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Transcription Factor CHOP
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Luciferases
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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MAP Kinase Kinase Kinase 3
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MAP Kinase Kinase Kinases
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MAP3K3 protein, human
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Map3k3 protein, mouse
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Caspases