TAK1, transforming growth factor β–activated kinase 1, also exerts a critical role in pro-inflammatory cytokine and TLR-mediated signaling pathways. The ubiquitin-activated TAK1 can phosphorylate IκB kinase (IKK) complex and p38, which leads to the activation of c-Jun N-terminal kinase (JNK), nuclear factor (NF)-κB, and MAPK signaling pathways.
TRAF6 could induce K63-dependent ubiquitination on TAK1 binding protein TAB2 and lead to TAK1 autophosphorylation. The polyubiquitin chains, which are synthesized by TRAF6 and Ubc13/Uev1A, could promote the autophosphorylation of TAK1 at Thr-184/187, leading to its activation.
We have find quinine which could combine with TRAF6 and inhibit the interaction between TRAF6 and Ubc13. So, we wanted to detect whether quinine can inhibit the activation of TAK1. |