MAP3K7


Mitogen-activated protein kinase kinase kinase 7 , also known as TAK1, is an enzyme that in humans is encoded by the MAP3K7 gene.

Function

The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase mediates signal transduction induced by TGF beta and morphogenetic protein, and controls a variety of cell functions including transcription regulation and apoptosis. TAK1 is a central regulator of cell death and is activated through a diverse set of intra- and extracellular stimuli. TAK1 regulates cell survival not solely through NF-κB but also through NF-κB-independent pathways such as oxidative stress and receptor-interacting protein kinase 1 kinase activity-dependent pathway. In response to IL-1, this protein forms a kinase complex including TRAF6, MAP3K7P1/TAB1 and MAP3K7P2/TAB2; this complex is required for the activation of nuclear factor kappa B. This kinase can also activate MAPK8/JNK, MAP2K4/MKK4, and thus plays a role in the cell response to environmental stresses. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.
This kinase has also been shown to regulate downstream cytokine expression such as TNF. Due to its regulation of TNF, TAK1 has become a novel target for the treatment of TNF mediated diseases such as auto immune disease but also other cytokine mediated disorders such as chronic pain and cancer. With the advent of novel selective TAK1 inhibitors, groups have explored the therapeutic potential of TAK1 targeted therapies. One group has shown that the selective TAK1 inhibitor, Takinib developed at Duke University attenuated rheumatoid arthritis like pathology in the CIA mouse model of human inflammatory arthritis. Furthermore, pharmacological inhibition of TAK1 has shown to reduce inflammatory cytokines in particular TNF.

Interactions

MAP3K7 has been shown to interact with: