Suggested pathway initiated by Cas III-ia leading to autophagy and apoptosis in C6 glioma cells. Cas III-ia may cause oxidative stress by JNK activation. JNK can phosphorylate Bcl-2 and release Beclin 1 enhancing autophagy. Alternatively, JNK can induce phosphorylation of c-jun; phospho-c-jun favors the production of AP-1 which, in turn, increases the expression of many genes among which are c-jun itself, Beclin, Atg7, Bax and FasL. Beclin 1 and Atg 7 may induce autophagy and FasL can stimulate Fas-R inducing the activation of caspase 8, which then degrades Bid into Bidt inducing Bax oligomerization and the depolarization of the mitochondrial membrane with release of cyt c and the consequent activation of caspase 3. Autophagy and apoptosis can thus induce cell death.
Trejo-Solís et al. BMC Cancer 2012 12:156 doi:10.1186/1471-2407-12-156