TAB1
Description
The TAB1 (TGF-beta activated kinase 1 (MAP3K7) binding protein 1) is a protein-coding gene located on chromosome 22.
TAB1 is an enzyme that regulates the MAP kinase kinase kinase MAP3K7/TAK1, which mediates signaling pathways triggered by TGF-beta, interleukin-1, and WNT-1. TAB1 interacts with and activates TAK1, with its C-terminal portion responsible for binding and activation, while a portion of the N-terminus acts as a dominant-negative inhibitor of TGF beta. This suggests TAB1 acts as a mediator between TGF beta receptors and TAK1. TAB1 can also activate MAPK14/p38alpha, offering an alternative activation pathway independent of MAPKK pathways. TAB1 contains multiple phosphorylation and ubiquitination sites and is important for skin homeostasis, wound repair, and oncogenesis.
TAB1 is a crucial adapter protein involved in the activation of JNK and NF-κB signaling pathways, leading to the production of proinflammatory cytokines in response to stimulation by toll-like receptors (TLRs) and cytokines. This function is achieved through its interaction with the catalytic domain of MAP3K7/TAK1, triggering autophosphorylation and complete activation of the kinase. Similarly, TAB1 associates with MAPK14, initiating its autophosphorylation and activation. In a feedback loop, MAPK14 phosphorylates TAB1, inhibiting MAP3K7/TAK1 activation. Additionally, TAB1 facilitates the recruitment of MAPK14 to the TAK1 complex, enabling the phosphorylation of the regulatory subunits TAB2 and TAB3.
TAB1 is also known as 3'-Tab1, MAP3K7IP1.
