TANK Antibody #2141

TRAFs (TNF receptor-associated factors) are a family of multifunctional adaptor proteins that bind to surface receptors and recruit additional proteins to form multiprotein signaling complexes capable of promoting cellular responses (1-3). Members of the TRAF family share a common carboxy-terminal "TRAF domain", which mediates interactions with associated proteins; many also contain amino-terminal Zinc/RING finger motifs. The first TRAFs identified, TRAF1 and TRAF2, were found by virtue of their interactions with the cytoplasmic domain of TNF-receptor 2 (TNFRII) (4). The six known TRAFs (TRAF1-6) act as adaptor proteins for a wide range of cell surface receptors and participate in the regulation of cell survival, proliferation, differentiation, and stress responses.
TRAF-associated NF-κB activator (TANK), also known as TRAF-interacting protein (I-TRAF), is a TRAF binding protein that demonstrates both stimulatory and inhibitory properties (5,6). TANK binds to the carboxy domain of the TRAF1, -2 and -3. Overexpression of TANK prevents the association of TRAF2 with TNFR2, inhibiting TNFR2 and CD40 induced NF-κB activation (6). TANK is also reported to synergize with low levels of TRAF2 to activate NF-κB (5). TANK assists in the activation of NF-κB via association and activation of TANK-binding kinase 1 (TBK1) or IKKε which promotes activation of the IKK complex (7,8). It has also been shown that TANK may synergize with TRAF2, TRAF5, and TRAF6 but not TRAF3 in SAPK activation (9). TNFα stimulation results in IKKβ-dependent phosphorylation of TANK which may provide negative feedback regulation of TANK mediated NF-κB activation (10).