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ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5
H Hsu1, I Solovyev, A Colombero
1Department of Cell Biology, Amgen Inc., Thousand Oaks, California 91320, USA. hhsu@amgen.com
Abstract:
Members of tumor necrosis factor receptor (TNFR) family signal largely through interactions with death domain proteins and TRAF proteins. Here we report the identification of a novel TNFR family member ATAR. Human and mouse ATAR contain 283 and 276 amino acids, respectively, making them the shortest known members of the TNFR superfamily. The receptor is expressed mainly in spleen, thymus, bone marrow, lung, and small intestine. The intracellular domains of human and mouse ATAR share only 25% identity, yet both interact with TRAF5 and TRAF2. This TRAF interaction domain resides at the C-terminal 20 amino acids. Like most other TRAF-interacting receptors, overexpression of ATAR activates the transcription factor NF-kappaB. Co-expression of ATAR with TRAF5, but not TRAF2, results in synergistic activation of NF-kappaB, suggesting potentially different roles for TRAF2 and TRAF5 in post-receptor signaling.
Insights
Researchers identified ATAR, the shortest known tumor necrosis factor receptor (TNFR) superfamily member. ATAR interacts with TRAF proteins, activating NF-kappaB, suggesting distinct signaling roles for TRAF2 and TRAF5.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- Tumor necrosis factor receptor (TNFR) superfamily members mediate cellular signaling pathways.
- These pathways often involve interactions with death domain and TRAF proteins.
Purpose of the Study:
- To identify and characterize novel members of the TNFR superfamily.
- To investigate the signaling mechanisms of a newly discovered TNFR member, ATAR.
Main Methods:
- Sequence analysis to identify novel TNFR family members.
- Expression analysis in various tissues.
- Co-immunoprecipitation assays to study protein interactions.
- Reporter assays to measure NF-kappaB activation.
Main Results:
- Identification of ATAR, the shortest known TNFR superfamily member.
- ATAR expression is prominent in immune organs (spleen, thymus, bone marrow) and lung, small intestine.
- ATAR interacts with TRAF2 and TRAF5 via its C-terminal 20 amino acids.
- ATAR activates NF-kappaB, with synergistic activation observed when co-expressed with TRAF5.
Conclusions:
- ATAR represents a novel, compact member of the TNFR superfamily.
- ATAR signaling involves TRAF protein interactions and NF-kappaB activation.
- Differential interaction with TRAF5 suggests distinct roles in downstream signaling pathways.