Tumor necrosis factor (TNF) induced signaling is mediated through association of TNF receptor (TNFR) with adaptor proteins, such as TNF receptor associated proteins (TRAFs). TRAFs form a family of cytoplasmic adapter proteins that mediate signal transduction from many members of the TNF-receptor superfamily (e. g. RANK, CD30, CD40, etc. ) and the interleukin-1 receptor. The carboxy-terminal region of TRAFs is required for self-association and interaction with receptor cytoplasmic domains following ligand-induced oligomerization. Recent molecular cloning studies have lead to identification of six TRAFs (TRAF1-TRAF6). TRAF3, originally named CRAF1, interacts directly with the CD40 cytoplasmic tail through a region of similarity to the tumor necrosis factor-alpha (TNF-alpha) receptor-associated factors. TRAF3 binds only a single site, which contains the sequence PEQET, whereas TRAF1 and TRAF2 are capable of binding to either the PEQET site or an additional downstream domain.View more View less
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