The fourth member of the TRAF protein family (TRAF4) presents several characteristics that distinguish it from the other members of the family. These characteristics concern the primary sequence of the protein, a strong evolutionary conservation, and a tightly regulated physiological...

The tumor necrosis factor receptor (TNFR) superfamily molecule CD40 is expressed by a wide variety of cell types following activation signals, and constitutively on B lymphocytes, macrophages, and dendritic cells. CD40 signals to cells stimulate kinase activation, gene expression, production...

TNF-receptor-associated factors (TRAFs) are intracellular proteins that bind to the cytoplasmic portion of TNF receptors and mediate downstream signaling. The six known TRAF proteins play overlapping yet distinct roles in controlling immune responses as well as cellular processes such as...

Tumor necrosis factor (TNF) receptor-associated factor (TRAF)1 was originally identified based on its ability to interact with the cytosolic domain of TNF receptor type 2 (TNFR2). TRAF1 is unique among TRAF proteins in that it lacks RING domain found in the N-terminal regions of other TRAFs....

The Ubiquitin-Proteasome Pathway Ubiquitin (Ub) is a highly conserved small polypeptide that is ubiquitously expressed in all eukaryotic cells. The best-known function of ubiquitin is to target protein degradation through covalent attachment of this polypeptide on protein substrates.1-3 This...

Members of the tumor necrosis factor (TNF) family govern many diverse physiological and cellular responses including cellular proliferation, differentiation, and apoptosis. Ligands of this family interact through a distinct set of specific receptors that lack enzymatic activity and therefore...

The tumor necrosis factor (TNF) receptor (TNFR) superfamily consists of over 20 type-I transmembrane proteins with conserved N-terminal cysteine-rich domains (CRDs) in the extracellular ligand binding region, which are specifically activated by the corresponding superfamily of TNF-like...

TRAF2 and TRAF5 are closely related members of the TRAF family of proteins. They are important signal transducers for a wide range of TNF receptor superfamily members, including TNFR1, TNFR2, CD40 and other lymphocyte costimulatory receptors, RANK/TRANCE-R, EDAR, LTbR, LMP-1 and IRE1. TRAF2 and...

Tumor necrosis factor (TNF) receptor (TNFR) associated factor 6 (TRAF6) is a unique member of the TRAF family of adaptor proteins that is involved in both the TNF receptor superfamily and the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily signal transduction pathways. The...

The lymphotoxin-b receptor (LTbR, TNFRSF3) signaling pathway activates gene transcription programs and cell death important in immune development and host defense. The TNF receptor associated factors (TRAF)-2, 3 and 5 function as adaptors linking LTbR signaling targets. Interestingly, TRAF...

TNF-Receptors Associated Factors (TRAFs) are the molecules that upon engagement of the TNF-receptor (TNFR) by a TNF-family ligand come first in contact with the activated TNFR, initially acting as docking molecules for kinases and other effector proteins that are recruited to the activated...

TRAF6 is divergent from other members of the TRAF family. Therefore, TRAF6 was expected to play physiological roles distinct from those of other TRAFs. In this chapter, we focused on the physiological functions specific to TRAF6 but not other TRAFs in immune system, formation of skin...

The TNF-Receptor Associated Factor (TRAF) domain (TD), also known as the meprin and TRAF-C homology (MATH) domain is a fold of seven anti-parallel b-helices that participates in protein-protein interactions. This fold is broadly represented among eukaryotes, where it is found associated...

Epstein-Barr Virus (EBV) Latent Infection Membrane Protein 1 (LMP1) is expressed in all the EBV related malignancies. LMP1 expression is critical for transformation of human B-cells by EBV. LMP1 expression in human B cells induces activation and adhesion molecule expression and cell...

Tumor necrosis factor receptor associated factor 3 (TRAF3) is one of the most enigmatic members in the TRAF family that consists of six members, TRAF1 to 6. Despite its similarities with other TRAFs in terms of structure and protein-protein association, overexpression of TRAF3 does not...