Dominant-negative c-Jun promotes neuronal survival by reducing BIM expression and inhibiting mitochondrial cytochrome c release
- Author(s)
- Whitfield, J; Neame, SJ; Paquet, L; Bernard, O; Ham, J;
- Details
- Publication Year 2001-03,Volume 29,Issue #3,Page 629-643
- Journal Title
- NEURON
- Publication Type
- Journal Article
- Abstract
- Sympathetic neurons require nerve growth factor for survival and die by apoptosis in its absence. Key steps in the death pathway include c-Jun activation, mitochondrial cytochrome c release, and caspase activation. Here, we show that neurons rescued from NGF withdrawal-induced apoptosis by expression of dominant-negative c-Jun do not release cytochrome c from their mitochondria. Furthermore, we find that the mRNA for BIM(EL), a proapoptotic BCL-2 family member, increases in level after NGF withdrawal and that this is reduced by dominant-negative c-Jun. Finally, overexpression of BIM(EL) in neurons induces cytochrome c redistribution and apoptosis in the presence of NGF, and neurons injected with sim antisense oligonucleotides or isolated from Bim(-/-) knockout mice die more slowly after NGF withdrawal.
- Publisher
- CELL PRESS
- Keywords
- PROGRAMMED CELL-DEATH; NERVE GROWTH-FACTOR; TROPHIC FACTOR DEPRIVATION; SYMPATHETIC NEURONS; BCL-2 FAMILY; FAS LIGAND; CASPASE ACTIVATION; APOPTOSIS; BAX; PROTEIN
- Publisher's Version
- https://doi.org/10.1016/S0896-6273(01)00239-2
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2001-03-01 12:00:00