A C-JUN DOMINANT-NEGATIVE MUTANT PROTECTS SYMPATHETIC NEURONS AGAINSTPROGRAMMED CELL-DEATH

Sympathetic neurons depend on nerve growth factor (NGF) for survival a nd die by apoptosis in its absence. We have investigated the pattern o f expression of the Jun and Fos family of transcription factors in dyi ng sympathetic neurons using antibodies specific for each family membe r. When sympathetic neurons are deprived of NGF, the level of c-Jun pr otein significantly increases, whereas the levels of the other members of the Jun and Fos family remain relatively constant. c-Jun also beco mes more phosphorylated, probably on its amino terminal transactivatio n domain. When microinjected into sympathetiic neurons, an expression vector for a c-Jun dominant negative mutant protects them against NGF withdrawal-induced death, indicating that AP-1 activity is essential f or neuronal cell death. Furthermore, overexpression of the full-length c-Jun protein is, in itself, sufficient to induce apoptosis in sympat hetic neurons.