TAB3 (D5J7D) Rabbit mAb #14241

TAK1 is a mitogen-activated protein kinase kinase kinase activated by TGF-β and various pro-inflammatory signals (1,2). In vivo, TAK1 activation requires its association with TAK1 binding protein 1 (TAB1), which triggers TAK1 autophosphorylation at Thr184 and Thr187 (3,4). The TAB2 adaptor protein links TAK1 with TRAF6 to mediate TAK1 activation following IL-1 stimulation (5). Once activated, TAK1 phosphorylates the MAPK kinases MKK4 and MKK3/6, which activate JNK and p38 MAPK, respectively. TAK1 and TRAF6 also activate the NF-κB pathway by phosphorylating the NF-κB inducing kinase (NIK) to trigger subsequent activation of IKK (2,6). In addition to TAK1, TAB1 interacts with and activates p38α MAPK (7). Targeted disruption of the TAB1 gene in mice causes a drastic reduction in TAK1 activity and leads to embryonic lethality (8).
TAK1-binding protein 3 (TAB3) is an additional binding partner for TAK1 and appears to be functionally redundant to TAB2 protein (9,10). The carboxy-terminal zinc finger domains in TAB2 and TAB3 bind to lysine 63-linked polyubiquitin chains within target proteins, including TRAF6, IKKγ, and RIP, which results in activation of IKK (11). Research studies also indicate that TAB2 and TAB3 proteins negatively regulate autophagy through interaction with beclin-1 (12,13).