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.
Pubmed ID: 15001576 RIS Download
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