   1.5.1.6 | physiological function |
FDH induces apoptosis in PC-3 prostate cells through simultaneous activation of the c-Jun-NH2-kinase JNK and extracellular signal-regulated kinase ERK pathways with JNK phosphorylating c-Jun and ERK1/2 phosphorylating Elk-1. The JNK1/2 inhibitor SP600125 or ERK1/2 inhibitor PD98059 prevents phosphorylation of c-Jun and Elk-1, correspondingly and partially protects PC-3 cells from FDH-induced cytotoxicity. Combination of the two inhibitors produces an additive effect. The FDH-induced apoptosis in p53-proficient A-549 cells also proceeds through activation of JNK1/2, but the down-stream target for JNK2 is p53 instead of c-Jun. In A-549 cells, FDH activates caspase 9, whereas in PC-3 cells, it activates caspase 8 |
713003 |
