TNF receptor-associated factor 5 (TRAF5) is an adapter protein and signal transducer that links members of the tumor necrosis factor receptor family to different signaling pathways by association with the receptor cytoplasmic domain and kinases. TRAF5 mediates activation of NF-kappa-B and probably JNK [, , , ]. TRAF5 contains a RING finger domain, five zinc finger domains, and a TRAF domain.
TNF receptor-associated factor 5 (TRAF5) is an adapter protein and signal transducer that links members of the tumor necrosis factor receptor family to different signaling pathways by association with the receptor cytoplasmic domain and kinases. TRAF5 mediates activation of NF-kappa-B and probably JNK [, , , ]. TRAF5 contains a RING finger domain, five zinc finger domains, and a TRAF domain.The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded β-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors [, ].
Tumor necrosis factor receptor superfamily member 8 (TNFRSF8), also known as CD30, Ki-1 or D1S166E, is expressed by activated T and B cells. It transduces signals that lead to the activation of NF-kappaB, mediated by the adaptor proteins TRAF2 and TRAF5 []. This receptor has been shown to limit the proliferative potential of auto-reactive CD8 effector T cells and protect the body against autoimmunity []. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. CD30 is expressed in malignant Hodgkin and Reed-Sternberg cells on the surface of extracellular vesicles, facilitating CD30-CD30L interaction between cell types []. This receptor is also associated with anaplastic large cell lymphoma. It is expressed in embryonal carcinoma, but not in seminoma, making it a useful marker in distinguishing between these germ cell tumors [, ]. Since CD30 has restricted expression in normal tissues, it is an optimal target for selectively eliminating CD30-expressing neoplastic cells by specific toxin-conjugated monoclonal antibodies (mAbs) [, ].This entry represents the N-terminal domain of TNFRSF8. TNF-receptors are modular proteins. The N-terminal extracellular part contains a cysteine-rich region responsible for ligand-binding. This region is composed of small modules of about 40 residues containing 6 conserved cysteines; the number and type of modules can vary in different members of the family [, , ].
Tumor necrosis factor receptor superfamily member 4 (TNFRSF4), also known as OX40, ACT35, CD134, IMD16 or TXGP1L, activates NF-kappaB through its interaction with adaptor proteins TRAF2 and TRAF5 []. It also promotes the expression of apoptosis inhibitors BCL2 and BCL2lL1/BCL2-XL, and thus suppresses apoptosis []. It is primarily expressed on activated CD4+ and CD8+ T cells, where it is transiently expressed and upregulated on the most recently antigen-activated T cells within inflammatory lesions. This makes it an attractive target to modulate immune responses, i.e. TNFRSF4 (OX40) blocking agents to inhibit adverse inflammation or agonists to enhance immune responses [, ]. An artificially created biologic fusion protein, OX40-immunoglobulin (OX40-Ig), prevents OX40 from reaching the T-cell receptors, thus reducing the T-cell response. Some single nucleotide polymorphisms (SNPs) of its natural ligand OX40 ligand (OX40L, CD252), which is also found on activated T cells, have been associated with systemic lupus erythematosus [].This entry represents the N-terminal domain of TNFRSF4. TNF-receptors are modular proteins. The N-terminal extracellular part contains a cysteine-rich region responsible for ligand-binding. This region is composed of small modules of about 40 residues containing 6 conserved cysteines; the number of modules can vary in number and type in different members of the family [, , ].
