MAPK and Notch-Mediated Effects of Meso-Xanthin F199 Compounds on Proliferative Activity and Apoptosis of Human Melanocytes in Three-Dimensional Culture

Figure 6

Comprehensive interaction of plenty proteins in signaling pathways inhibited by FX exposure. The protein PSME1 is one of the main regulators of IL-1, in response to which, in turn, the expression of PTGIS is enhanced. The interaction of IL-1 with its single receptor IL1R causes the dissociation of IRAK1 and IRAK4 from the complex with Myd88 and the assembling of a molecular complex with IL-1. This complex, in turn, activates TRAF6, which starts the process of its autoubiquitination. Being in such modified form, TRAF6 interacts with TAK1, which has to be already activated by the TGF-β factor. After interaction and activation, TAK1 is bound to a complex of TAK2 and TAK3 subunits and such molecular machinery enhances the expression of the NF-κB inhibitors, like IKK2 and IKKB. On the other hand, PSME1 is a regulator of the Raf-MAPK pathway where IL-1 interacts with Ras surface receptors and, thus, activates its cytoplasmic GEF domain. Activated RAF with GTP can interfere with the YWHAB dimer, and the PHB factor initiates their rearrangement and further heterodimerization, which is the starting point for triggering the MAPK/MAPK2 signaling pathway.