| 内容提要: |
TRAF6, a unique member of the TRAF family, is an adaptor for the signals induced by the interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) superfamily and plays a critical role in innate immune responses. The RING domain of TRAF6 functions together with the E2 Ubc13/Uev1A complex to mediate AKT and TAK1 activations. AKT has been shown to promote cell survival by growth factors against several apoptotic stimuli and possesses a significant role not only in tumor development but also in the tumor’s potential response to cancer treatment. On the other hand, 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.
So, if we can find the compound which can bind to TRAF6, it will inhibit the activation of AKT and TAK1. Therefore, the compound could inhibit the proliferation of tumor cell and induce the early apoptosis of the cells. |