Tumor necrosis factor (TNF) receptor-associated factors (TRAF) are signaling proteins that participate in many aspects of the signal transduction of the immune receptors, including receptors for TNF and related cytokines, the IL-1 receptor, Toll-like receptors (TLR), and the B cell receptors (BCR). TRAF activation eventually leads to activation of transcription factors such as NFκB and AP-1. The N-terminal part of TRAFs 2-7 consists of a new gene (RING) type zinc binding domain followed by several CCHC zinc fingers. TRAF1 lacks the most N-terminal RING domain, but retains one predicted CCHC zinc finger. The zinc finger family has expanded rapidly to mediate protein-DNA, protein-RNA, protein-protein, and protein-lipid interactions. All TRAF proteins, except TRAF7, share the characteristic TRAF domain, or merpin and TRAF homology (MATH) domain at their C-termini, which mediates interaction with receptors and adaptor proteins. The C-terminal TRAF domain can be further divided into TRAF-N and TRAF-C domains. The TRAF-N domain is a coiled-coil region that mediates homo- and hetero-oligomerization among TRAF family members. The TRAF-C domain is responsible for physical association with upstream receptors and adaptor proteins. Each TRAF-C domain adopts a unique α-sandwich topology composed of eight anti-parallel β strands, which is similar to the conformation observed in merpin metalloproteases and the Drosophila Siah protein. TRAF6 is the major transducer of IL-1 receptor/TLR signaling. Ligation of IL-1 to IL-1R first recruits myeloid differentiation primary response gene 88 via the interaction between the Toll/interleukin receptor domains (TIR) present in both IL-1R cytoplasmic tail and MyD88. MyD88 then recruits IL-1 receptor-associated kinase 1 (IRAK1) and its homolog IRAK4 via death domain (DD)-DD interactions.
|Title of host publication||Handbook of Cell Signaling, 2/e|
|Number of pages||7|
|Publication status||Published - 2010|
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)