ABSTRACT
Different JNK isoforms may play distinct roles in apoptosis. While Jnk l'JnkZ *' mice ex hibited impaired apoptosis in certain brain regions,23,25 mice had normal neuronal development.28 Interestingly, sympathetic neurons isolated from both mice were resistant to apoptosis induced by NGF withdrawal or kainate treatment.22 It is possible that JNK1 and JNK2, but not JNK3, are involved in developmental neuronal apoptosis, but all three JNK isoforms are involved in neuronal apoptosis induced by environmental stresses. It has yet to be determined why the neuronal specific JNK3 is not involved in neuronal apoptosis during de velopment.28 The proapoptotic effect of JNK1/JNK2 in neuronal development is unlikely mediated by c-Jun, since there were no obvious defects in developmental neuronal apoptosis in c - ju n 1' mice.29 In fibroblasts, JNK1 and JNK2 play opposite roles in TNF-OC or UV-induced apoptosis. TNF-OC or UV induced apoptosis was suppressed in Jn k l'1' fibroblasts but enhanced in J n k l1' cells, due to the differentia regulation of these two JNK isoforms by TNF-OC and UV (see discussion below).27
