ATAR, a Novel Tumor Necrosis Factor Receptor Family Member, Signals through TRAF2 and TRAF5*

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-κB. Co-expression of ATAR with TRAF5, but not TRAF2, results in synergistic activation of NF-κB, suggesting potentially different roles for TRAF2 and TRAF5 in post-receptor signaling.

[1]  D. Goeddel,et al.  A death-domain-containing receptor that mediates apoptosis , 1996, Nature.

[2]  A. Chinnaiyan,et al.  Signal Transduction by DR3, a Death Domain-Containing Receptor Related to TNFR-1 and CD95 , 1996, Science.

[3]  Michael Karin,et al.  Dissection of TNF Receptor 1 Effector Functions: JNK Activation Is Not Linked to Apoptosis While NF-κB Activation Prevents Cell Death , 1996, Cell.

[4]  David Baltimore,et al.  NF-κB: Ten Years After , 1996, Cell.

[5]  Zhaodan Cao,et al.  TRAF6 is a signal transducer for interleukin-1 , 1996, Nature.

[6]  S. Lee,et al.  CD30/TNF receptor-associated factor interaction: NF-kappa B activation and binding specificity. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[7]  S. Srinivasula,et al.  In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[8]  C. Ware,et al.  TRAF5, an Activator of NF-κB and Putative Signal Transducer for the Lymphotoxin-β Receptor* , 1996, The Journal of Biological Chemistry.

[9]  David Wallach,et al.  Involvement of MACH, a Novel MORT1/FADD-Interacting Protease, in Fas/APO-1- and TNF Receptor–Induced Cell Death , 1996, Cell.

[10]  Matthias Mann,et al.  FLICE, A Novel FADD-Homologous ICE/CED-3–like Protease, Is Recruited to the CD95 (Fas/APO-1) Death-Inducing Signaling Complex , 1996, Cell.

[11]  D. Baltimore,et al.  TANK, a co-inducer with TRAF2 of TNF- and CD 40L-mediated NF-kappaB activation. , 1996, Genes & development.

[12]  Hong-Bing Shu,et al.  TRADD–TRAF2 and TRADD–FADD Interactions Define Two Distinct TNF Receptor 1 Signal Transduction Pathways , 1996, Cell.

[13]  P. Basset,et al.  Presence of a New Conserved Domain in CART1, a Novel Member of the Tumor Necrosis Factor Receptor-associated Protein Family, Which Is Expressed in Breast Carcinoma (*) , 1995, The Journal of Biological Chemistry.

[14]  D. Goeddel,et al.  TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40 , 1995, Science.

[15]  D. Baltimore,et al.  Involvement of CRAF1, a relative of TRAF, in CD40 signaling , 1995, Science.

[16]  D. Goeddel,et al.  A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor , 1994, Cell.

[17]  Terry Farrah,et al.  The TNF receptor superfamily of cellular and viral proteins: Activation, costimulation, and death , 1994, Cell.

[18]  L. Tartaglia,et al.  A novel domain within the 55 kd TNF receptor signals cell death , 1993, Cell.

[19]  S. Nagata,et al.  A novel protein domain required for apoptosis. Mutational analysis of human Fas antigen. , 1993, The Journal of biological chemistry.