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Updated: Aug 26, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
TRAF7 potentiates MEKK3-induced AP1 and CHOP activation and induces apoptosis
Liang-Guo Xu1, Lian-Yun Li, Hong-Bing Shu
1Integrated Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, Colorado 80206, USA.
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.
Insights
Researchers identified TRAF7, a novel tumor necrosis factor receptor-associated factor (TRAF). TRAF7 interacts with MEKK3, influencing AP1 and CHOP activation and inducing apoptosis.
Area of Science:
- Molecular Biology
- Cell Signaling
- Immunology
Background:
- Tumor necrosis factor receptor-associated factor (TRAF) proteins are key mediators in signaling pathways.
- TRAF family members regulate NF-kappaB, JNK, and p38 activation downstream of TNF and TIR receptors.
- Most TRAF proteins possess a functional N-terminal RING finger domain.
Purpose of the Study:
- To identify and characterize novel members of the TRAF protein family.
- To investigate the role of a newly identified TRAF protein, TRAF7, in cellular signaling pathways.
- To elucidate the functional domains of TRAF7 involved in MEKK3 signaling and apoptosis induction.
Main Methods:
- Protein identification and domain analysis.
- Co-immunoprecipitation assays to study protein interactions.
- Antisense RNA technology for gene silencing.
- Overexpression studies and domain mapping for functional analysis.
Main Results:
- A novel TRAF protein, TRAF7, was identified, featuring a RING finger, zinc finger, and seven WD40 repeats.
- TRAF7 specifically interacts with MEKK3, enhancing MEKK3-mediated AP1 and CHOP activation.
- TRAF7 depletion via antisense RNA abrogated MEKK3-induced AP1 and CHOP activation.
- Overexpression of TRAF7 triggered caspase-dependent apoptosis, with distinct domains mediating signaling and apoptosis.
Conclusions:
- TRAF7 is a novel member of the TRAF family, playing a significant role in MEKK3 signaling.
- TRAF7 is implicated in the regulation of AP1 and CHOP activation.
- TRAF7 contributes to the induction of apoptosis through specific functional domains.
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