TRAF2 signal pathway networks. TRAF2 promotes canonical NF-κB pathway, and suppresses noncanonical NF-κB pathway [45, 46, 50, 51]. TNF-R1 activates the canonical NF-κB pathway via recruiting TRADD, which in turn binds adaptor proteins TRAF2, TRAF5 and RIP1 . These adaptor protein complexes activate the IKK (IκB kinase) proteins for NF-κB (p65/p50 heterodimer) activation, following phosphorylation and degradation of the inhibitory protein IκBα [45, 46]. On contrary, LTβR (Lymphotoxin β receptor) promotes noncanonical NF-κB signaling pathway bypassing activation of the pro-apoptotic caspase cascades, but directly recruiting TRAF2 and TRAF3. IKKα homodimers are then activated through the upstream NIK (NFκB inducing kinase). IKKα induces NF-κB p100 precursor phosphorylation, followed by partially processing to a p52 form for leading to noncanonical NF-κB (p52/ RelB heterodimer) activation [45, 46].