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A working model for the role of Lys63-linked TAK1 polyubiquitination in TNFα- and IL-1β-mediated IKK/NF-κB and JNK/AP-1 activation. TNFα and IL-1β induces TAK1 polyubiquitination at Lys158 residue and phosphorylation at the Thr178, Thr184, Thr187, and Ser192 residues for TAK1 activation. In turn, activated TAK1 mediates IKK/NF-κB and JNK/AP-1 activation as well as NF-κB- and AP-1-dependent IL-6 gene expression in the cells.
