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.
Xu
Liang-Guo
LG
Integrated Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, Colorado 80206, USA.
Li
Lian-Yun
LY
Shu
Hong-Bing
HB
D000595:Amino Acid Sequence; D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology*; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D053938:DNA Fragmentation; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D048748:MAP Kinase Kinase Kinase 3; D020930:MAP Kinase Kinase Kinases / Q000737:chemistry*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D018808:Transcription Factor AP-1 / Q000502:physiology*; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000502:physiology*; D014162:Transfection; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D016335:Zinc Fingers; D048051:p38 Mitogen-Activated Protein Kinases
D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; C497249:DDIT3 protein, human; D018124:Receptors, Tumor Necrosis Factor; C486460:TRAF7 protein, human; C486461:Traf7 protein, mouse; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D051742:Transcription Factor CHOP; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048748:MAP Kinase Kinase Kinase 3; D020930:MAP Kinase Kinase Kinases; C482625:MAP3K3 protein, human; C482626:Map3k3 protein, mouse; D020169:Caspases