Figure 5.
The antiapoptotic effect of GPx1 upregulation promotes cell survival in some cancers. ASK-1 is maintained in an inactive state by its association with the redox-sensitive thioredoxin (Trx). TNFα-induced oxidative stress can promote the oxidation of thioredoxin, leading to the association of TRAF2 and ASK1 oligomers. These active complexes promote JNK-mediated pathways of apoptosis. In some cancer cells, the presence of GPx1 can decrease the oxidation of Trx to keep ASK-1 in an inactive state. Furthermore, association of GPx1 with TRAF2 may prevent the formation of active ASK1/TRAF2 complexes to block JNK activation and apoptosis. Other mechanisms may promote cells survival in other types of cancer, as discussed in the text.